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Background: Reversion mutations of somatic BRCA mutations are an important source of resistance within ovarian cancer. Furthermore, these reversion mutations are known to change over the course of treatment. Better understanding of the mechanisms leading to reversion mutations and the role of serial ctDNA collection in detecting changes to overall landscape of resistance mutations over time is needed to guide treatment in the metastatic setting. Methods: Here we study a case of metastatic ovarian cancer undergoing multiple lines of treatment with collection of three serial ctDNA samples. These samples were analyzed by Guardant Health next generation sequencing to detect somatic alterations and their associated mutant allele frequency (MAF) as % cfDNA. Results: Analysis of our initial ctDNA collection, taken during PARP-inhibitor therapy, revealed a nonsense BRCA-1 mutation (c. 2563C > T p. Q855∗), consistent with the BRCA 1 somatic mutation detected on tumor tissue analysis. Initial analysis also revealed a reversion mutation (c.2535_2576del) resulting in an in-frame deletion of the somatic BRCA-1 alteration. The second collection, taken while still on PARP-inhibitor therapy, re-demonstrated this indel reversion mutation along with a second indel reversion mutation (c.2546_2587del), again resulting in an in-frame deletion of the somatic BRCA-1 mutation. The final ctDNA, collected upon initiation of immunotherapy, revealed 4 novel SNV reversion mutations (c.2564A > C, c.2564A > T, c.2565G > T, and c.2565G > C). These SNV reversion mutations result in missense amino acid changes rather than insertions or deletions within the BRCA-1 somatic mutation. The previous indel reversion mutations were no longer detected. Conclusions: This study illustrates the role of serial ctDNA analyses in the detection of resistance mutations and the dynamic nature of reversion mutations with multiple lines of treatment. While other studies have described both indels and SNVs that occur in tandem, a change in the types of reversion mutations detected across changing therapies has never before been described. Further studies regarding the unique selective pressures arising from use of multiple types of therapy is needed to fully explain this phenomenon.

Evidence-based guidelines on the management of pain associated with first-trimester medical abortion are lacking. Most published clinical trials have failed to report on this important aspect of the procedure. The aim of this comprehensive work was to provide clinical advice based on a comprehensive literature review, supplemented by the clinical experience of a group of European experts in case no evidence is available. Pain level ranged from 5 to 8 in 80% of studies where pain was measured on a 0-10 visual analogue scale; severe pain was reported by 20-80% of women. Pain assessment was rarely reported in studies. Pain treatment should be preventive and avoidance of unnecessary uterine contractions should be considered. Analgesic treatment should follow the WHO three-step ladder, starting with the use of NSAIDs and allowing for easily available back-up treatment with weak opioids. [ABSTRACT FROM AUTHOR]

Dental implant surgeries involve the insertion of implant fixtures into alveolar bones to replace missing teeth. When the availability of alveolar bone at the surgical site is insufficient, bone graft particles are filled in the insertion site for successful bone reconstruction. Bone graft particles induce bone regeneration over several months at the insertion site. Subsequently, implant fixtures can be inserted at the recipient site. Thus, conventional dental implant surgery is performed in several steps, which in turn increases the treatment period and cost involved. Therefore, to reduce surgical time and minimize treatment costs, a novel hybrid scaffold filled with bone graft particles that could be combined with implant fixtures is proposed. This scaffold is composed of a three-dimensionally (3D) printed polycaprolactone (PCL) frame and osteoconductive ceramic materials such as hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP). Herein, we analyzed the porosity, internal microstructure, and hydrophilicity of the hybrid scaffold. Additionally, Saos-2 cells were used to assess cell viability and proliferation. Two types of control scaffolds were used (a 3D printed PCL frame and a hybrid scaffold without HA/β-TCP particles) for comparison, and the fabricated hybrid scaffold was verified to retain osteoconductive ceramic particles without losses. Moreover, the fabricated hybrid scaffold had high porosity and excellent microstructural interconnectivity. The in vitro Saos-2 cell experiments revealed superior cell proliferation and alkaline phosphatase assay results for the hybrid scaffold than the control scaffold. Hence, the proposed hybrid scaffold is a promising candidate for minimizing cost and duration of dental implant surgery.

Abstract Background There is little information regarding lay-people's representations of influenza and influenza-like illness in their day-to-day lives. An insight into these views may aid our understanding of community attitudes regarding official recommendations for its prevention. Methods This was a qualitative research. Semi-structured face-to-face interviews were conducted with 40 French participants from the community, and from five different locations. Questions elicited the participants' representations of onset of flu and influenza-like illness, as well as their views on what can/should be done to deal with symptoms and their personal experience with flu and flu-like symptoms. Results Thematic content analyses allowed us to identify five main themes: the presence of a clear continuum between influenza-like illness and flu; a description of flu as a very contagious disease; flu as being benign, except in "frail people", which the respondents never considered themselves to be; interruption of daily activities, which could be considered pathognomonic for influenza for most subjects; self-medication as the main current practice, and requests for healthcare mainly to confirm an auto-diagnosis. Conclusions There was a large homogeneity in the representation of flu. There was also a gap between people's representations (i.e., a continuum from having a "cold" to having "influenza") and scientific knowledge (i.e., a distinction between "true" influenza and influenza-like illnesses based on the existence of a confirmatory virological diagnosis). This gap raises issues for current campaigns for flu prevention, as these may not be congruent with the representation of flu being responsible for interrupting daily activities while also being seen as a non-severe disease, as well as the perception that flu is only a risk to "frail people" though no participants considered themselves to be "frail".

Recent terrorist assaults have demonstrated the need for the exploration and design of sustainable and stable chemical sensors with quick reaction times combined with great sensitivity. Among several classes of chemical warfare agents, nerve agents have been proven to be the most hazardous. Even short-term exposure to them can result in severe toxic effects. Human beings inadvertently face the after-effects of these chemicals even several years after these chemicals were used. Due to the extreme toxicity and difficulty in handling, dimethyl methylphosphonate (DMMP), a simulant of nerve agents with much lesser toxicity, is frequently used in laboratories as a substitute. Having a chemical structure almost identical to those of nerve agents, DMMP can mimic the properties of nerve agents. Through this paper, authors have attempted to introduce the evolution of several chemical sensors used to detect DMMP in recent years, including field-effect transistors, chemicapacitors, chemiresistors, and mass-sensitive sensors. A detailed discussion of the role of nanomaterials as chemical sensors in the detection of DMMP has been the main focus of the work through a comprehensive overview of the research on gas sensors that have been reported making use of the properties of a wide range of nanomaterials., 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 Elsevier B.V. All rights reserved.)

Over the years, bioaccumulation of hazardous chemicals in the food chain has become a critical issue, resulting in numerous health risks. Environmental mitigation aims to clean up contaminated sites and eliminate hazardous materials from the air, water, or soil to restore the site to its original and safe condition. Pesticides constitute one of the most dangerous environmental pollutants which are generally used to increase crop production. Addressing the removal or treatment of pesticides has become pivotal in mitigating environmental threats. Diverse remediation methods are employed to protect the environment and public health. Graphene-based materials have emerged as promising candidates with exceptional properties, including excellent adsorption capacity due to their high surface area, strong hydrophilicity, and tunable properties. Owing to these properties, they have been attracting major research attention in the field of design and fabrication of materials for the mitigation of pesticides from the environment such as from contaminated food, water and other samples. Various physical, chemical and biological extraction techniques are adopted to remove pesticides. This review article provides an insight into the potential role of graphene-based materials in the environmental remediation of pesticides. We have focused on the removal of Organophosphates, Organochlorines, Carbamates and Pyrethroids present in water, fruit, vegetable and other samples, highlighting the urgent need for environmental remediation. While graphene-based materials hold potential for pesticide remediation, addressing challenges in scalable production, assessing long-term sustainability, and mitigating potential environmental impacts are critical steps for successful large-scale applications., 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 Elsevier B.V. All rights reserved.)

Groundwater, a vital global resource, is essential for sustaining life and various human activities. However, its quality and availability face increasing threats from both natural and human-induced factors. Widespread contamination, arising from both natural origins and human activities such as agriculture, industry, mining, improper waste disposal, and wastewater release, poses significant risks to human health and water security. India, known for its dense population and pronounced groundwater challenges, serves as a prominent case study. Notably, in most of its regions, groundwater resources have been found to be severely contaminated by various chemical, biological, and radioactive contaminants. This review presents an examination of contamination disparities across various states of semi-arid and cold regions, encompassing diverse assessment methods. The studies conducted in semi-arid regions of North, South, West, and East India highlight the consistent presence of fluorides and nitrates majorly, as well as heavy metals in some areas, with values exceeding the permissible limits recommended by both the Bureau of Indian Standards (BIS) and the World Health Organization (WHO). These contaminants pose skeletal and dental threats, methemoglobinemia, and even cancer. Similarly, in cold regions, nitrate exposure and pesticide residues, reportedly exceeding BIS and WHO parameters, pose gastrointestinal and other waterborne health concerns. The findings also indicated that the recommended limits of several quality parameters, including pH, electrical conductivity, total dissolved solids (TDS), total hardness, and total alkalinity majorly surpassed. Emphasising the reported values of the various contaminant levels simultaneously with addressing the challenges and future perspectives, the review unravels the complex landscape of groundwater contamination and its health-related implications in semi-arid and cold regions of India., Competing Interests: Declaration of competing interest The authors declare no competing financial interests that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Among various classes of antibiotics, fluoroquinolones, especially Levofloxacin, are being administered on a large scale for numerous purposes. Being highly stable to be completely metabolized, residual quantities of Levofloxacin get accumulated into the food chain proving a great global threat for aquatic as well as terrestrial ecosystems. Various removal techniques including both conventional and advanced methods have been reported for this purpose. This review is a novel attempt to make a critical analysis of the recent advances made exclusively toward the sequestration of Levofloxacin from wastewater through an extensive literature survey (2015-2021). Adsorption and advanced oxidation processes especially photocatalytic degradation are the most tested techniques in which assorted nanomaterials play a significant role. Several photocatalysts exhibited up to 100% degradation of LEV which makes photocatalytic degradation the best method among other tested methods. However, the degraded products need to be further monitored in terms of their toxicity. Biological degradation may prove to be the most environment-friendly with the least toxicity, unfortunately, not much research is reported in the field. With these key findings and knowledge gaps, authors suggest the scope of hybrid techniques, which have been experimented on other antibiotics. These can potentially minimize the disadvantages of the individual techniques concurrently improving the efficiency of LEV removal. Besides, techniques like column adsorption, membrane treatment, and ozonation, being least reported, reserve good perspectives for future research. With these implications, the review will certainly serve as a breakthrough for researchers working in this field to aid their future findings., Competing Interests: Declaration of competing interest The authors declare no competing financial interests that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Researchers nowadays are relentlessly on a race exploring sustainable materials and techniques for the sequestration of toxic dyes and metal ions from water bodies. Biopolymers such as guar gum, owing to its high abundance, low cost and non-toxicity, are potential candidates in this field. Plenty of hydroxyl groups in the polymer backbone enable guar gum to be functionalised or grafted in a versatile manner proving itself as an excellent starting substance for fabricating upgraded materials meant for diverse applications. This review offers a comprehensive coverage of the role of guar gum-based nanocomposites in removal of dyes and heavy metal ions from waste water through adsorption and photo-catalytic degradation. Isotherm and kinetics models, fabrication routes, characterisation techniques, swelling properties and reusability as well as adsorption and degradation mechanisms are outlined. A detailed analysis with convincing results suggests a good future perspective of implementation of these materials in real-time wastewater treatment technology., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To record the definition and management of Very Early Medical Abortion (VEMA) in different countries., Study Design: An Internet survey was circulated internationally among providers of medical abortion via a website. The questionnaire focused on reasons for performing or delaying medical abortion at a very early gestational age and the perceived advantages and disadvantages of VEMA., Results: Out of 220 completed questionnaires, 50 % came from European abortion providers (n = 110). Most respondents (72 %) defined VEMA as abortion performed in the presence of a positive hCG pregnancy test but with an empty uterine cavity or a gestational sac-like structure, and no signs or symptoms of ectopic pregnancy. A total of 74 % of respondents thought it was not necessary to wait for a diagnosis of intrauterine pregnancy before starting medical abortion. Equally, 74 % were aware of the possibility of an ectopic pregnancy., Conclusion: According to European providers of medical abortion, waiting for the diagnosis of an intrauterine pregnancy is not necessary and does not improve treatment of ectopic pregnancy. Providers should know that medical abortion can be performed effectively and safely as soon as the woman has decided. There is no lower gestational age limit., Competing Interests: Declaration of Competing Interest The authors were all members of the external scientific advisory board of Exelgyn at the time of this study. Christian Fiala has served on an ad hoc basis as an invited lecturer for Exelgyn. Aubert Agostini is a board member at Nordic Pharma and MSD, and an investigator for some Nordic Pharma studies. Teresa Bombas is a member of advisory boards for Merck and HRA, has an occasional consultancy relationship with Exelgyn and Nordic, and is a speaker at conferences/symposiums organized by Bayer, Merck, HRA, Gedeon, and Exelgyn. Roberto Lertxundi has a financial relationship (member of advisory boards, lecturer, and/or consultant) with Exelgyn, Nordic-Pharma, Exeltis, Bayer-Pharma, and Teva. Marek Lubusky has an occasional consultancy relationship with Exelgyn and Nordic. Mirella Parachini has an occasional consultancy relationship with Exelgyn and Nordic. Kristina Gemzell-Danielsson has served on an ad hoc basis as an invited lecturer for Exelgyn, Line Pharma, and Gynuity, and as an investigator in clinical trials conducted by Concept Foundation/SunPharma. Laurence Saya is an employee of Altius Pharma CS, and as such was indirectly paid by Exelgyn for help in medical writing., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Medical termination of pregnancy (MToP, or medical abortion) is a highly effective method with a reported efficacy of 95-98%. However, different criteria are currently used to define success, and there are different recommendations for the treatment of what is considered a failure of MToP. This work was undertaken to develop a consensus around a set of well-defined MToP outcomes, as recommended by the Core Outcomes in Women's and Newborn Health initiative., Methods: A literature search was made of national and international guidelines and of recommendations of expert groups for various outcomes of MToP and subsequent management. Based on a review of the findings, a group of European experts in MToP undertook a consensus process to agree on a set of core MToP outcomes., Results: The following core MToP outcomes were defined: success, failure (ongoing pregnancy), need for additional treatment (medical or surgical) to complete MToP (missed abortion, incomplete abortion), complications and the woman's request for additional treatment (medical or surgical). Recommendations for the management of unsuccessful outcomes were also formulated., Conclusion: New definitions of MToP outcomes that are more focused on objective criteria and consequently less dependent on provider interpretation are proposed. This should allow better comparison of the efficacy of different regimens and improve the management of failed or incomplete abortion.

Objectives: To evaluate pain and other early adverse events associated with different regimens of medical abortion up to nine weeks of amenorrhoea., Methods: The literature was searched for comparative studies of medical abortion using mifepristone followed by the prostaglandin analogue misoprostol. Publications, which included pain assessment were further analysed., Results: Of the 1459 publications on medical abortion identified, only 23 comparative, prospective trials corresponded to the inclusion criteria. Patients in these studies received different dosages of mifepristone in combination with different dosages of misoprostol administered via diverse routes or at various intervals. Information on pain level was reported in 12/23 papers (52%), information regarding systematic administration of analgesics in 12/23 articles (52%) and information concerning analgesia used was available for only 10/23 studies (43%)., Conclusions: Neither pain nor its treatment are systematically reported in clinical trials of medical abortion; this shortcoming reflects a neglect of the individual pain perception. When data are mentioned, they are too inconsistent to allow for any comparison between different treatment protocols. Standardised evaluation of pain is needed and the correlation between the dosage of misoprostol and the intensity of pain must be assessed in future studies.

A highly diastereo- and chemoselective intramolecular nickel-catalyzed cycloaddition of alkene- and alkyne-tethered alkynylidenecyclopropanes is reported. The method constitutes the first fully intramolecular [3 + 2 + 2] alkylidenecyclopropropane cycloaddition occurring via a proximal cleavage of the cyclopropane and makes it possible to build relevant 6,7,5-tricyclic frameworks in a single-pot reaction. Importantly, the reaction outcome is highly dependent on the characteristics of the nickel ligands.

The complex [OsTp(kappa(1)-OCMe)(2)(P(i)Pr(3))]BF(4) [Tp = hydridotris(pyrazolyl)borate] promotes the cleavage of both C(sp(3))-C(sp(2)) bonds of benzylidenecyclopropane and 3-phenylpropylidenecyclopropane to yield the complexes [OsTp(=C=CHR)(eta(2)-CH(2)=CH(2))(P(i)Pr(3))]BF(4) (R = Ph, CH(2)CH(2)Ph). The process is proposed to take place via metallacyclopropene intermediates stabilized by an ethylene chelation assistant. The driving force for the fragmentation is the high stability of the resulting ethylene-Os-vinylidene species.

Alkylidenecyclopropanes containing a chelation assistant at the terminal carbon atom of the olefinic moiety undergo an Os- or Ru-promoted ring expansion reaction to afford metal cyclobutylidene derivatives. The process occurs through a novel mechanism that implies a 1,2-migration of a CH(2) group of the three-membered ring from an olefinic carbon atom to the other one. It takes place, without direct participation of the metal, on a metallaheterocyclopentene intermediate which is generated from an eta(2)-methylenecyclopropane species stabilized by coordination of the chelation assistant.

Objective. To challenge psychiatrists about their practice regarding patients' treatment adherence in severe mental disease, and make them discuss possible ways to improve this through their relationship with patients. Methods. A total of 423 physicians from 32 countries were assigned across 41 parallel groups during a workshop organised on adherence in severe mental diseases. Factors that influence adherence, and questions and measures to help patient-clinician interaction were discussed and rated. Results. The most important factor influencing adherence to treatment was considered to be insight. The factor over which clinicians felt they had the greatest influence was the therapeutic relationship. The question that most physicians considered the most useful for improving communication with patients was, "Does taking medication cause any problems for you?" Additional areas identified as important in improving adherence included addressing the positive and negative aspects of medication, patient expectations and what patients hoped to gain from seeing their physician. Intervention programmes to improve adherence included patient education, motivational interviewing and cognitive-behavioural therapy. A composite toolkit based on the top-rated questions to improve communication with patients and measures to aid adherence was recommended. Conclusion. Patient-centred practice is fundamental to ensuring adherence in mentally ill patients. Working tools can be successfully developed in interactive workshop settings, through reviewing and challenging current clinical practice.

A method was developed for detection of low numbers of African trypanosomes in whole blood. The method is based on selective lysis of erythrocytes and leukocytes by aerolysin, a toxin produced by the bacterium Aeromonas hydrophila. African trypanosomes do not bind the toxin and their viability and motility are therefore unaffected by this treatment.

In a previous report, we described the selection and partial characterization of three distinct classes of methotrexate (Mtx)-resistant Chinese hamster ovary cells (CHO) (1). Class I cells contained a structural alteration in dihydrofolate reductase. Class II cells showed a alteration affecting the permeability of the drug. Class III cells, selected from class I cells, had an increased activity of the altered enzyme. In the work described here, the sensitivity of these lines to the diaminopyrimidines has been investigated. Class I cells are as sensitive, class II cells are 5- to 10-fold more sensitive, and class III cells are 10- to 30-fold more resistant than wild-type cells. The increased sensitivity of the class II cells provided an opportunity to select for revertants of these mutants and such phentotypic wild-type revertant cells have been selected using one diaminopyrimidine, pyrimethamine. Such cells have drug sensitivities and permeability characteristics similar to wild-type cells. A second class has been identified which has wild-type drug sensitivities to the diaminopyrimidines but Mtx class II resistance to Mtx, and drug permeabilities characteristic of Mtx-resistant class II cells.