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Background: Mental disorders can have a significant impact on patients' life, including economic, social and individual consequences, and psychotropic medication is essential to treat these conditions. Psychotropic drug utilization studies contribute to a clearer picture of the management of these conditions. Data published from Romania on this topic is limited. The present study aims to characterize the utilization patterns of anxiolytics, antidepressants (ADs), and antipsychotics (APs) in Romania during 1998-2018. Methods: Drug utilization data were provided by Management Center for Documentation, Information and Marketing (CEGEDIM) Romania and quantitative data for each psychotropic medicine were converted to total defined daily doses (DDDs) and to DDD/1000inhabitants/day (DDD/TID). The total use of medicines in DDD/TID was computed in order to obtain the drug utilization 90% (DU90%) segment. Results: An increasing trend in total utilization of psychotropic medicines in Romania started in 2004. Anxiolytics use was predominant until 2013 and the yearly anxiolytic use over the entire study period remained between 10 and 15 DDD/TID. Diazepam lost popularity over time in detriment of the utilization of other anxiolytic benzodiazepines, such as alprazolam and lorazepam. ADs utilization markedly increased during the study period (the average annual growth rate was 13.66% starting 1999). Selective serotonin reuptake inhibitors (SSRIs) became present on the 2008 DU90% and was the dominant class of ADs, with sertraline being the most prescribed, followed by escitalopram and paroxetine. APs utilization showed an increasing trend from 2003 until 2018. Atypical APs became present on the 2008 DU90%, while typical APs were no longer included in the 2018 DU90%. Among atypical APs, olanzapine was the main agent prescribed, and starting 2010 was followed by quetiapine and risperidone. The uptake of APs long-acting formulations became more evident during the last analyzed years (2015-2018). Conclusion: We observed an increasing utilization of APs and a more prominent increase in ADs utilization in Romania during 1998-2018. The anxiolytic prescribing remained nearly stable during this time. Further research can bring more information on the various factors influencing psychotropic utilization in Romania., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Iaru, Bucsa, Farcas, Pop, Cristina, Armean, Brumboiu, Vostinaru and Mogosan.)

Background: Clinical trials that evaluated interventions to prevent postthrombotic syndrome (PTS) used the Villalta scale (VS) to define PTS, but there is a lack of consistency in its use., Objectives: This study aimed to improve the ability to identify patients with clinically meaningful PTS after DVT in participants of the ATTRACT trial., Methods: We conducted a post hoc exploratory analysis of 691 patients from the ATTRACT study, a randomized trial evaluating the effectiveness of pharmacomechanical thrombolysis to prevent PTS in proximal deep vein thrombosis. We compared 8 VS approaches to classify patients with or without PTS in terms of their ability to discriminate between those with poorer vs better venous disease-specific quality of life (Venous Insufficiency Epidemiological and Economic Study Quality of Life [VEINES-QOL]) between 6- and 24-months follow-up. The difference in the average area under the fitted curve of VEINES-QOL scores between PTS and no PTS ( Δ A U C ¯ ) were compared among approaches., Results: For any PTS (a single VS score ≥5), approaches 1 to 3 had similar Δ A U C ¯ (-21.2, -23.7, -22.0, respectively). Adjusting the VS for contralateral chronic venous insufficiency (CVI) or restricting to patients without baseline CVI (approaches 7 and 8) did not improve Δ A U C ¯ (-13.6, -19.9, respectively; P >.01). For moderate-to-severe PTS (a single VS score ≥10), approaches 5 and 6 requiring 2 positive assessments had greater but not statistically significant Δ A U C ¯ than approach 4, using one single positive assessment (-31.7, -31.0, -25.5, respectively; P >.01)., Conclusion: A single VS score of ≥ 5 reliably distinguishes patients with clinically meaningful PTS as assessed by impact on QOL and is preferred because of greater convenience (only one assessment needed). Alternative methods to define PTS (ie, adjusting for CVI) do not improve the scale's ability to identify clinically meaningful PTS., (© 2022 The Authors.)

Antibiotic resistance (AR) is a naturally occurring phenomenon with the capacity to render useless all known antibiotics in the fight against bacterial infections. Although bacterial resistance appeared before any human life form, this process has accelerated in the past years. Important causes of AR in modern times could be the over-prescription of antibiotics, the presence of faulty infection-prevention strategies, pollution in overcrowded areas, or the use of antibiotics in agriculture and farming, together with a decreased interest from the pharmaceutical industry in researching and testing new antibiotics. The last cause is primarily due to the high costs of developing antibiotics. The aim of the present review is to highlight the techniques that are being developed for the identification of new antibiotics to assist this lengthy process, using artificial intelligence (AI). AI can shorten the preclinical phase by rapidly generating many substances based on algorithms created by machine learning (ML) through techniques such as neural networks (NN) or deep learning (DL). Recently, a text mining system that incorporates DL algorithms was used to help and speed up the data curation process. Moreover, new and old methods are being used to identify new antibiotics, such as the combination of quantitative structure-activity relationship (QSAR) methods with ML or Raman spectroscopy and MALDI-TOF MS combined with NN, offering faster and easier interpretation of results. Thus, AI techniques are important additional tools for researchers and clinicians in the race for new methods of overcoming bacterial resistance.

Background: Pharmacogenetics (PGx) is an important component of personalized medicine that has the potential to improve medicines' effectiveness and safety. However, despite progress in technology and availability, PGx testing application into patient-care in Eastern Europe countries, has been slow. Objectives: Our aim was to describe knowledge and attitudes of Romanian pharmacists concerning PGx, and identify potential factors limiting PGx implementation. Method: An anonymous, web-based questionnaire was distributed to Romanian pharmacists registered in the National Pharmacists' Association (NPA) via an official e-mail sent by NPA representatives. Results: A total of 1,058 pharmacists completed the questionnaires, resulting in a response rate of 7.6%. Pharmacists were predominantly female (90.1%), younger than 49 years (87.5%) and mostly worked in community pharmacies (80.2%). Most pharmacists (64.8%) had a knowledge score between 30 and 49 points out of 60, and (75.4%) had attitude scores between 9 and 7 out of 10. Attitude and knowledge scores positively correlated. Conclusion: Despite performing fairly well on general questions regarding PGx, Romanian pharmacists may lack in-depth knowledge, which can affect their readiness to discuss PGx information with patients or other healthcare professionals. High pricing was considered an important impediment in PGx implementation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pop, Cristina, Iaru, Popa and Mogoșan.)

The monitoring of the daily life activities routine is beneficial, especially in old age. It can provide relevant information on the person's health state and wellbeing and can help identify deviations that signal care deterioration or incidents that require intervention. Existing approaches consider the daily routine as a rather strict sequence of activities which is not usually the case. In this paper, we propose a solution to identify flexible daily routines of older adults considering variations related to the order of activities and activities timespan. It combines the Gap-BIDE algorithm with a collaborative clustering technique. The Gap-BIDE algorithm is used to identify the most common patterns of behavior considering the elements of variations in activities sequence and the period of the day (i.e., night, morning, afternoon, and evening) for increased pattern mining flexibility. K-means and Hierarchical Clustering Agglomerative algorithms are collaboratively used to address the time-related elements of variability in daily routine like activities timespan vectors. A prototype was developed to monitor and detect the daily living activities based on smartwatch data using a deep learning architecture and the InceptionTime model, for which the highest accuracy was obtained. The results obtained are showing that the proposed solution can successfully identify the routines considering the aspects of flexibility such as activity sequences, optional and compulsory activities, timespan, and start and end time. The best results were obtained for the collaborative clustering solution that considers flexibility aspects in routine identification, providing coverage of monitored data of 89.63%.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive form of pancreatic malignancy which occurs in over 90% of such cases. Pancreaticoduodenectomy (PD) is used with a curative purpose for localized PDAC. Case presentation: A 68-year-old woman presented to our service through a transfer from another service, to be investigated and treated for a head of the pancreas tumor in a tertiary referral hospital. After a complete clinical and paraclinical evaluation, the patient was diagnosed with a PDAC and also with a median arcuate ligament syndrome (MALS). The surgical treatment was considered adequate, therefore, the patient underwent a PD with transmesocolic hepaticojejunostomy, pancreaticogastric anastomosis, precolic end-to-side gastrojejunostomy, Witzel jejunostomy and with the help of the cardiovascular surgery team from the Heart Institute, Cluj- Napoca, an aortohepatic bypass using saphenous vein graft was performed. Conclusion: Bypass was essential because the blood flow in the proper hepatic artery was not restored after sectioning the median arcuate ligament and clamping the gastroduodenal artery. The patient had a favorable outcome. The particularity of the present case consists of the complete occlusion of the celiac trunk by MALS and the total vascularization of the supramesocolic organs due to the superior mesenteric artery through the gastroduodenal artery., (Celsius.)

Functional dyspepsia represents one of the most common and prevalent disorders of the brain-gut interaction, with a large number of widespread risk factors being identified. With an intricate pathogenesis and symptomatology, it heavily impacts the quality of life and, due to the limited efficacy of traditional pharmacological agents, patients are likely to seek other medical and non-medical solutions to their problem. Over the last few years, significant research in this domain has emphasized the importance of various psychological therapies and nutritional recommendations. Nevertheless, a correlation has been established between functional dyspepsia and food intolerances, with more and more patients adopting different kinds of exclusion diets, leading to weight loss, restrictive eating behaviour and an imbalanced nutritional state, further negatively impacting their quality of life. Thus, in this systematic review, we aimed at analysing the impact and efficiency of certain exclusion diets undertook by patients, more precisely, the gluten-free diet and the low-FODMAP diet.

Background: The Inuit people residing in Nunavik, Quebec, are vulnerable to major trauma owing to environmental and social factors; however, there is no systematic data collection for trauma in Nunavik, and, apart from data regarding patients who are transferred to tertiary care centres, no data enter the Quebec trauma registry directly from Nunavik. We performed a study to characterize the epidemiologic features of trauma in Nunavik, and describe indications for transfer and outcomes of patients referred to the tertiary trauma centre., Methods: We collected data retrospectively for all patients with trauma admitted to the Centre de santé Tulattavik de l'Ungava in Kuujjuaq from 2005 to 2014. Sociodemographic, injury and health services data were extracted. The data were analyzed in conjunction with coroners' reports on death from trauma in Nunavik., Results: A total of 797 trauma cases were identified. The most common causes of injury were motor vehicle collisions (258 cases [32.4%]), falls (137 [17.2%]) and blunt assault (95 [11.9%]). One-third of patients (262 [32.9%]) were transferred to the tertiary care centre in Montréal. The incidence rate of major trauma (Injury Severity Score > 12) was 18.1 and 21.7 per 10 000 person-years in the Kuujjuaq region and the Puvirnituq region, respectively, which translates to a relative risk (RR) of 4 compared to the Quebec population. The disparity observed in trauma mortality rate was even greater, with an RR of 47.6 compared to the Quebec population., Conclusion: The study showed major disparity in trauma incidence and mortality rate between Nunavik and the province of Quebec. Our findings allow for a better understanding of the burden of injury and regional trauma mortality in Nunavik, and recommendations for optimization of the trauma system in this unique setting., Competing Interests: Competing interests: None declared., (© 2021 CMA Joule Inc. or its licensors.)

This article draws upon qualitative ethnographic data collected between 2005 and 2013 in southern Romania among women who have been consistently using abortion as a contraceptive method. It particularly considers the role that lived religion might have played in some individuals' strategies to render abortion a justifiable practice. Over the last seven decades, Romanian women's experiences of abortion have often been at odds with both secular and religious regulations. This study shifts the perspective from the biopolitics and the bioethics of abortion toward women's own reproductive decision-making strategies in a context of enduring traditional patriarchy. It explores the fluid and pragmatic ways in which some Romanians use the notions of "God's will," "sin," "redemption," "afterlife," and "Godparenting" to redefine abortion as a partially disembodied reproductive event. As a reproductive decision-making resource, lived religion empowers women to navigate the lived complexities of conception and contraception.

This article locates the symbolic construction of "corrupted purity"-as a key assertion in Romanian parents' HPV vaccination refusal narratives-within a multiplicity of entangled rumors concerning reproduction and the state. Romania's unsuccessful HPV vaccination campaign is not unique. However, the shifting discourses around purity and corruption-through which some parents conveyed anxieties about their daughters being targeted for the vaccine-place a particular twist on the Romanian case of resisting the HPV vaccination. Parental discourses took the form of clusters of rumors about state medicine's failure to provide adequate reproductive health care, additive-laden foods, and exposure to radioactive contamination. In these rumors, corruption becomes literally embodied, through ingestion, consumption, contact, or inoculation. Parental discourses about what is being injected into their daughters' pristine bodies express their uncertainty around navigating the unsettled post-socialist medical landscape., (© 2016 by the American Anthropological Association.)

The use of robots in therapy for children with autism spectrum disorder (ASD) raises issues concerning the ethical and social acceptability of this technology and, more generally, about human-robot interaction. However, usually philosophical papers on the ethics of human-robot-interaction do not take into account stakeholders' views; yet it is important to involve stakeholders in order to render the research responsive to concerns within the autism and autism therapy community. To support responsible research and innovation in this field, this paper identifies a range of ethical, social and therapeutic concerns, and presents and discusses the results of an exploratory survey that investigated these issues and explored stakeholders' expectations about this kind of therapy. We conclude that although in general stakeholders approve of using robots in therapy for children with ASD, it is wise to avoid replacing therapists by robots and to develop and use robots that have what we call supervised autonomy. This is likely to create more trust among stakeholders and improve the quality of the therapy. Moreover, our research suggests that issues concerning the appearance of the robot need to be adequately dealt with by the researchers and therapists. For instance, our survey suggests that zoomorphic robots may be less problematic than robots that look too much like humans.

Advanced metastatic disease is difficult to manage and specific therapeutic targets are rare. We showed earlier that metastatic breast cancer cells use the activated conformer of adhesion receptor integrin alphavbeta3 for dissemination. We now investigated if targeting this form of the receptor can impact advanced metastatic disease, and we analyzed the mechanisms involved. Treatment of advanced multi-organ metastasis in SCID mice with patient-derived scFv antibodies specific for activated integrin alphavbeta3 caused stagnation and regression of metastatic growth. The antibodies specifically localized to tumor lesions in vivo and inhibited alphavbeta3 ligand binding at nanomolar levels in vitro. At the cellular level, the scFs associated rapidly with high affinity alphavbeta3 and dissociated extremely slowly. Thus, the scFvs occupy the receptor on metastatic tumor cells for prolonged periods of time, allowing for inhibition of established cell interaction with natural alphavbeta3 ligands. Potential apoptosis inducing effects of the antibodies through interaction with caspase-3 were studied as potential additional mechanism of treatment response. However, in contrast to a previous concept, neither the RGD-containing ligand mimetic scFvs nor RGD peptides bound or activated caspase-3 at the cellular or molecular level. This indicates that the treatment effects seen in the animal model are primarily due to antibody interference with alphavbeta3 ligation. Inhibition of advanced metastatic disease by treatment with cancer patient derived single chain antibodies against the activated conformer of integrin alphavbeta3 identifies this form of the receptor as a suitable target for therapy.

The measurement of general caspase activity and the quantification of purified recombinant caspases in vitro can be accomplished with relative ease. But the determination of which caspases are active in a cellular context is much more challenging. This is because commercially available small molecule substrates and inhibitors do not display sufficient specificity to dissect the complex interplay of caspase pathways. Here we describe procedures that can be used to validate which caspases are active in cell culture models and determine which caspases are responsible for specific cleavage events. We also recommend methods for working with recombinant initiator caspases in vitro and suggest ways to accurately assess the cleavage efficiency of natural caspase substrates.