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Introduction The empty pelvis syndrome is a significant source of morbidity following pelvic exenteration surgery. It remains poorly defined with research in this field being heterogeneous and of low quality. Furthermore, there has been minimal engagement with patient representatives following pelvic exenteration with respect to the empty pelvic syndrome. ‘PelvEx—Beating the empty pelvis syndrome’ aims to engage both patient representatives and healthcare professionals to achieve an international consensus on a core outcome set, pathophysiology and mitigation of the empty pelvis syndrome.Methods and analysis A modified-Delphi approach will be followed with a three-stage study design. First, statements will be longlisted using a recent systematic review, healthcare professional event, patient and public engagement, and Delphi piloting. Second, statements will be shortlisted using up to three rounds of online modified Delphi. Third, statements will be confirmed and instruments for measurable statements selected using a virtual patient-representative consensus meeting, and finally a face-to-face healthcare professional consensus meeting.Ethics and dissemination The University of Southampton Faculty of Medicine ethics committee has approved this protocol, which is registered as a study with the Core Outcome Measures in Effectiveness Trials Initiative. Publication of this study will increase the potential for comparative research to further understanding and prevent the empty pelvis syndrome.Trial registration number NCT05683795.

Glioblastoma (GBM) is an aggressive, common brain cancer known to disrupt redox biology, affecting behavior and DNA integrity. Past research remains inconclusive. To further understand this, an investigation was conducted on physical training’s effects on behavior, redox balance, and genomic stability in GBMA models. Forty-seven male C57BL/6J mice, 60 days old, were divided into GBM and sham groups (n = 15, n = 10, respectively), which were further subdivided into trained (Str, Gtr; n = 10, n = 12) and untrained (Sut, Gut; n = 10, n = 15) subsets. The trained mice performed moderate aerobic exercises on a treadmill five to six times a week for a month while untrained mice remained in their enclosures. Behavior was evaluated using open-field and rotarod tests. Post training, the mice were euthanized and brain, liver, bone marrow, and blood samples were analyzed for redox and genomic instability markers. The results indicated increased latency values in the trained GBM (Gtr) group, suggesting a beneficial impact of exercise. Elevated reactive oxygen species in the parietal tissue of untrained GBM mice (Gut) were reduced post training. Moreover, Gtr mice exhibited lower tail intensity, indicating less genomic instability. Thus, exercise could serve as a promising supplemental GBM treatment, modulating redox parameters and reducing genomic instability.

Mutations in the Budding uninhibited by benzimidazoles (BUB1) gene were recently associated with neurodevelopmental disorders (Carvalhal et al., 2022). Here, we describe the generation and characterization of two induced pluripotent stem cells (iPSC) clones from a young female with microcephaly. The patient carried two variants in the BUBfibroblast gene (OMIM # 602452), one (c.[2197dupG]; p.[D732fs*11]) paternally inherited and one (c.[2625+1G>A]; p.[V822_L875del] maternally inherited. The generated clones exhibit a normal karyotype (UALGi003-A) and trisomy 8 (UALGi003-B), express pluripotency markers, and differentiate into trilineage cells in vitro. These cell lines can be used to study neurodevelopment and the processes of chromosome segregation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Peritoneal sarcomatosis is a rare malignant disease with a poor prognosis, secondary to peritoneal dissemination of abdominopelvic soft tissue sarcomas. Its rarity, together with the characteristic histological heterogeneity and the historically poor response to systemic treatments, has prevented the establishment of widely accepted treatment criteria with curative intent. In this sense, radical cytoreductive surgery (CRS) with peritonectomy procedures and hyperthermic intraperitoneal chemotherapy (HIPEC), widely used in peritoneal carcinomatosis with excellent results, have not had the same evolutionary development in patients with peritoneal sarcomatosis. A multidisciplinary working group of experts in sarcomas and peritoneal oncological surgery established a series of recommendations based on current scientific evidence for the management of peritoneal sarcomatosis, taking into account the different histological subgroups of abdominopelvic sarcomas that can cause it depending on their origin: retroperitoneal sarcomas, uterine sarcomas, and visceral/peritoneal sarcomas of GIST (gastrointestinal stromal tumor) and non-GIST origin. This article shows the results of sarcoma experts' voting on the recommendations presented during the I Ibero-American Consensus on the Management of Peritoneal Sarcomatosis, which took place during the recent celebration of the III Hispanic-Portuguese Meeting for Updates on the Treatment of Sarcomas.

Introduction: The lack of human resources for disease prevention and control is evident in times of health crisis, such as the COVID-19 pandemic. In public health emergencies, the capacity for adequate assistance and guaranteed access to pharmacological treatment are fundamental and contribute to impact reduction. We aimed to analyze the profile, performance, and characteristics related to the self-perception of preparedness among pharmacists who responded to the COVID-19 pandemic in Brazil., Method: A cross-sectional study was conducted in two stages: content validation of a questionnaire and its application to a representative sample of pharmacists in Rio de Janeiro. The snowball technique was used to recruit participants. A logistic regression model was adjusted to determine the effects of the factors on the probability of a pharmacist feeling prepared to act during the pandemic., Results: Six experts approved and validated the questionnaire, and 376 pharmacists were included in the study, 60.6 % of whom were in places specially designated by health authorities to diagnose and treat COVID-19. Professionals participated in various activities related to pandemic demands, including medication management and population guidance. Postgraduate degrees increased the odds of participants feeling prepared to act during the pandemic. Furthermore, pharmacists who worked in reference facilities were more likely to feel ready than those who worked in other places. Professionals who knew treatment guidelines were almost three times more likely to feel prepared than the ones without the knowledge of treatment guidelines. Training or guidance on how to act during the pandemic increased pharmacists' odds of feeling prepared by 2.58 times., Conclusion: Pharmacists actuated from diagnosis to treatment and participated in the health activities required during the pandemic. Factors contributing to the self-perception of preparedness were identified. Such factors can be targets for interventions to promote the preparedness of the workforce for future health emergencies., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Skin metastases are an important co-morbidity in melanoma. Despite broad adoption, electrochemotherapy implementation is hindered by a lack of treatment indications, uncertainty regarding procedural aspects, and the absence of quality indicators. An expert consensus may harmonize the approach among centres and facilitate comparison with other therapies., Methods: An interdisciplinary panel was recruited for a three-round e-Delphi survey. A literature-based 113-item questionnaire was proposed to 160 professionals from 53 European centres. Participants rated each item for relevance and degree of agreement on a five-point Likert scale, and received anonymous controlled feedback to allow revision. The items that reached concordant agreement in two successive iterations were included in the final consensus list. In the third round, quality indicator benchmarks were defined using a real-time Delphi method., Results: The initial working group included 122 respondents, of whom 100 (82 per cent) completed the first round, thus qualifying for inclusion in the expert panel (49 surgeons, 29 dermatologists, 15 medical oncologists, three radiotherapists, two nurse specialists, two clinician scientists). The completion rate was 97 per cent (97 of 100) and 93 per cent (90 of 97) in the second and third rounds respectively. The final consensus list included 54 statements with benchmarks (treatment indications, (37); procedural aspects, (1); quality indicators, (16))., Conclusion: An expert panel achieved consensus on the use of electrochemotherapy in melanoma, with a core set of statements providing general direction to electrochemotherapy users to refine indications, align clinical practices, and promote quality assurance programmes and local audits. The residual controversial topics set future research priorities to improve patient care., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Objectives: Kaposi's sarcoma (KS) is a locally aggressive mesenchymal tumor that involves the lymphovascular system, with a tendency to become multifocal. Electrochemotherapy (ECT) is considered a valuable treatment option in selected patients with cutaneous and subcutaneous KS lesions., Methods: We report a retrospective study that included 14 classic and endemic KS patients that underwent ECT sessions for the treatment of KS cutaneous and subcutaneous lesions at our institution., Results: According to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, our patients had an overall response rate (ORR) of 100% to the ECT treatment. A complete response (CR) was obtained in 92.8% of patients after one or more ECT sessions. Only one patient had a progressive disease (PD). The treatment was well tolerated with a low complication rate, mainly transitory local pain or skin ulceration., Conclusions: ECT represents a locoregional therapy for containment and symptomatic control of classic and endemic KS cutaneous and subcutaneous lesions. Further studies including different subtypes of KS patients should also be performed., (© 2022 the International Society of Dermatology.)

Teachers can contribute to preventing and solving cyberbullying situations. Therefore, it is relevant to investigate what may influence their involvement and actions concerning this phenomenon. A first study analyze teachers' definitions of cyberbullying, how they would intervene and feel morally implicated with the phenomenon. A second study aimed to investigate the association between teachers' being aware of cyberbullying and their perceived severity, moral disengagement with the phenomenon, perceived performance to solve such situations and their acquired knowledge about cyberbullying. Twenty semi-structured interviews were conducted in the first study with 25 to 65-year-old teachers. An online inventory was answered in study two by 541 middle and high school teachers ( M age = 50, SD = 7). A thematic analysis from the first study revealed that most teachers did not report repetition of behavior, power imbalance, intentionality to harm, and occurrence among peers as defining features of cyberbullying. Also, strategies they would use to intervene mainly focused on reporting the incident. Moreover, moral disengagement mechanisms were found in teachers' discourse, which contribute to displacing responsibility for intervening and perceiving cyberbullying as less severe. In the second study, path analysis revealed that teachers' awareness of cyberbullying among their students was positively associated with moral disengagement and acquired knowledge of the phenomenon. The mediating role of acquired knowledge of cyberbullying was significant between being aware of cyberbullying and teachers' perceived severity of the situation, moral disengagement, and perceived performance to solve these situations. These findings highlight the relevance of developing cyberbullying training actions involving teachers.

Budding uninhibited by benzimidazoles (BUB1) contributes to multiple mitotic processes. Here, we describe the first two patients with biallelic BUB1 germline mutations, who both display microcephaly, intellectual disability, and several patient-specific features. The identified mutations cause variable degrees of reduced total protein level and kinase activity, leading to distinct mitotic defects. Both patients’ cells show prolonged mitosis duration, chromosome segregation errors, and an overall functional spindle assembly checkpoint. However, while BUB1 levels mostly affect BUBR1 kinetochore recruitment, impaired kinase activity prohibits centromeric recruitment of Aurora B, SGO1, and TOP2A, correlating with anaphase bridges, aneuploidy, and defective sister chromatid cohesion. We do not observe accelerated cohesion fatigue. We hypothesize that unresolved DNA catenanes increase cohesion strength, with concomitant increase in anaphase bridges. In conclusion, BUB1 mutations cause a neurodevelopmental disorder, with clinical and cellular phenotypes that partially resemble previously described syndromes, including autosomal recessive primary microcephaly, mosaic variegated aneuploidy, and cohesinopathies.

Anorectal malignant melanoma (AMM) is a rare malignant tumor. Surgery remains the gold standard but new adjuvant treatments to allow local sphincter-saving are warranted. Electrochemotherapy (ECT) is an alternative to surgery in selected cohorts of patients. To evaluate safety and efficacy of ECT in a retrospective series of patients with primary or recurrent AMM in terms of local disease control, local progression free and overall survival. Seven primary and one recurrent AMM underwent ECT. Patients were followed at 1 and 2 months and at the longest available follow-up with clinical examination and/or ultrasound. One month after ECT 6/8 (75%) patients showed complete response, 1/8 partial response (12.5%) and 1/8 stable disease (12.5%), confirmed at 2 months. Bleeding stopped in all patients, and pain was absent or mild/moderate in all patients. No serious adverse events were observed. At 1 year of follow-up seven out of eight patients were alive (87.5%), four were disease-free and three were alive with disease. At the longest available follow-up (mean 4.9 ± 2.0 years) five out of eight (62.5%) of patients were still alive. Our study showed that ECT is well tolerated and effective in the treatment of patients with anal melanoma with good local control of disease., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Epidermolysis Bullosa (EB) is a rare group of diseases caused by genetic variants in skin structural proteins. EB is characterized by varying degrees of skin fragility, blisters and impaired wound healing, and is classified based on the ultrastructural levels of skin cleavage-simplex, junctional, dystrophic, and Kindler Syndrome. Squamous cell carcinoma (SCC) is the most severe complication and most common cause of death of patients with EB, particularly in those with recessive dystrophic Epidermolysis Bullosa (RDEB). To date, the first line of treatment of SCC in patients with RDEB is surgery, despite the high risk of recurrence. Radiotherapy and systemic therapy have been avoided due to its skin toxicity. Recently, electrochemotherapy (ECT) has been proposed as a potential treatment. We report eight sessions of ECT using bleomycin for treatment of SCC in five patients with EB. After 8 weeks all patients showed an objective response. Four patients (seven ECT sessions) had a complete response. The treatment was well tolerated, with mild adverse effects, such as local pain, erythema, and ulceration. Our results demonstrate that ECT is a potential treatment for SCC in patients with RDEB., (© 2020 Wiley Periodicals LLC.)

Sister chromatid cohesion mediated by cohesin is essential for mitotic fidelity. It counteracts spindle forces to prevent premature chromatid individualization and random genome segregation. However, it is unclear what effects a partial decline of cohesin may have on chromosome organization. In this study, we provide a quantitative analysis of cohesin decay by inducing acute removal of defined amounts of cohesin from metaphase-arrested chromosomes. We demonstrate that sister chromatid cohesion is very resistant to cohesin loss as chromatid disjunction is only observed when chromosomes lose >80% of bound cohesin. Removal close to this threshold leads to chromosomes that are still cohered but display compromised chromosome alignment and unstable spindle attachments. Partial cohesin decay leads to increased duration of mitosis and susceptibility to errors in chromosome segregation. We propose that high cohesin density ensures centromeric chromatin rigidity necessary to maintain a force balance with the mitotic spindle. Partial cohesin loss may lead to chromosome segregation errors even when sister chromatid cohesion is fulfilled., (© 2018 Carvalhal et al.)

Asymmetric cell divisions depend on the precise placement of the spindle apparatus. In mammalian oocytes, spindles assemble close to the cell's center, but chromosome segregation takes place at the cell periphery where half of the chromosomes are expelled into small, nondeveloping polar bodies at anaphase. By dividing so asymmetrically, most of the cytoplasmic content within the oocyte is preserved, which is critical for successful fertilization and early development. Recently we determined that the nucleoporin ALADIN participates in spindle assembly in somatic cells, and we have also shown that female mice homozygously null for ALADIN are sterile. In this study we show that this protein is involved in specific meiotic stages, including meiotic resumption, spindle assembly, and spindle positioning. In the absence of ALADIN, polar body extrusion is compromised due to problems in spindle orientation and anchoring at the first meiotic anaphase. ALADIN null oocytes that mature far enough to be fertilized in vitro are unable to support embryonic development beyond the two-cell stage. Overall, we find that ALADIN is critical for oocyte maturation and appears to be far more essential for this process than for somatic cell divisions., (© 2017 Carvalhal, Stevense, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).)

Introduction: Centrally inserted central catheter (CICC) insertion is a commonly performed procedure that may give rise to different complications. Despite the suggestion of guidelines to use ultrasound guidance (USG) for vascular access, not all centers use it systematically. The aim of this study is to illustrate the experience with ultrasound in CICC placement at a high-volume oncological center, in a country where the landmark technique is standard., Methods: Retrospective analysis of a prospective database was performed on CICC placement under USG in the Central Venous Catheter Unit of Instituto Português de Oncologia de Lisboa Francisco Gentil, from 2012 to 2015., Results: Three thousand five hundred and seventy-two procedures were recorded. From 2728 CICC placements, 1187 (43.5%) were done using USG. The majority of CICC placements were successful without immediate complications (96.1%). In 55 cases (4.6%), more than three attempts were necessary to puncture the vein. Pneumothorax occurred in 5 cases (0.4%) and arterial puncture was registered in 41 cases (3.5%). An increasing use of USG for placing CICCs was planned and observed over the years and, in the last year of the study, 67.3% of the CICC placements were with USG., Conclusions: CICC placement with USG is a safe and effective technique. Despite some resistance that is observed, these results support that it is worth following the guidelines that advocate the use of the USG in the placement of CICC.

Microbial mats are complex, micro-scale ecosystems that can be found in a wide range of environments. In the top layer of photosynthetic mats from hypersaline environments, a large diversity of cyanobacteria typically predominates. With the aim of strengthening the knowledge on the cyanobacterial diversity present in the coastal lagoon system of Araruama (state of Rio de Janeiro, Brazil), we have characterized three mat samples by means of a polyphasic approach. We have used morphological and molecular data obtained by culture-dependent and -independent methods. Moreover, we have compared different classification methodologies and discussed the outcomes, challenges, and pitfalls of these methods. Overall, we show that Araruama's lagoons harbor a high cyanobacterial diversity. Thirty-six unique morphospecies could be differentiated, which increases by more than 15% the number of morphospecies and genera already reported for the entire Araruama system. Morphology-based data were compared with the 16S rRNA gene phylogeny derived from isolate sequences and environmental sequences obtained by PCR-DGGE and pyrosequencing. Most of the 48 phylotypes could be associated with the observed morphospecies at the order level. More than one third of the sequences demonstrated to be closely affiliated (best BLAST hit results of ≥99%) with cyanobacteria from ecologically similar habitats. Some sequences had no close relatives in the public databases, including one from an isolate, being placed as "loner" sequences within different orders. This hints at hidden cyanobacterial diversity in the mats of the Araruama system, while reinforcing the relevance of using complementary approaches to study cyanobacterial diversity.

PHD1 (also known as EGLN2) belongs to a family of prolyl hydroxylases (PHDs) that are involved in the control of the cellular response to hypoxia. PHD1 is also able to regulate mitotic progression through the regulation of the crucial centrosomal protein Cep192, establishing a link between the oxygen-sensing and the cell cycle machinery. Here, we demonstrate that PHD1 is phosphorylated by CDK2, CDK4 and CDK6 at S130. This phosphorylation fluctuates with the cell cycle and can be induced through oncogenic activation. Functionally, PHD1 phosphorylation leads to increased induction of hypoxia-inducible factor (HIF) protein levels and activity during hypoxia. PHD1 phosphorylation does not alter its intrinsic enzymatic activity, but instead decreases the interaction between PHD1 and HIF1α. Interestingly, although phosphorylation of PHD1 at S130 lowers its activity towards HIF1α, this modification increases the activity of PHD1 towards Cep192. These results establish a mechanism by which cell cycle mediators, such as CDKs, temporally control the activity of PHD1, directly altering the regulation of HIF1α and Cep192., (© 2016. Published by The Company of Biologists Ltd.)

The formation of the mitotic spindle is a complex process that requires massive cellular reorganization. Regulation by mitotic kinases controls this entire process. One of these mitotic controllers is Aurora A kinase, which is itself highly regulated. In this study, we show that the nuclear pore protein ALADIN is a novel spatial regulator of Aurora A. Without ALADIN, Aurora A spreads from centrosomes onto spindle microtubules, which affects the distribution of a subset of microtubule regulators and slows spindle assembly and chromosome alignment. ALADIN interacts with inactive Aurora A and is recruited to the spindle pole after Aurora A inhibition. Of interest, mutations in ALADIN cause triple A syndrome. We find that some of the mitotic phenotypes that we observe after ALADIN depletion also occur in cells from triple A syndrome patients, which raises the possibility that mitotic errors may underlie part of the etiology of this syndrome., (© 2015 Carvalhal et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).)