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Objectives: The study investigated the difficulties experienced by endodontics researchers around the world in conducting studies and writing papers. Materials and Methods: A survey consisting of 18 questions on the difficulties experienced by endodontics researchers in performing studies and writing papers was e-mailed to academics in the field of endodontics working at 202 universities. The independent risk factors were analyzed using binary logistic regression at a significance level of 0.05. Results: A total of 581 individuals (10.7%) agreed to participate in the study. Almost half the participants (48.2%) reported that they had received some type of training in conducting studies and writing papers. In response to the question, “Do you get help from a statistician to perform the statistical analyses of your studies?,” 77.1% answered “yes.” Around 40% of the participants stated that the need to obtain ethical approval negatively affected their desire to conduct studies. The participants’ regions had no effect on the reported difficulties associated with writing papers in English or conducting statistical analyses (p > 0.05). Most participants (81.8%) reported difficulties in writing the Discussion section, regardless of their region, academic degrees, or years of experience. Conclusions: The participants stated they experienced difficulties in many areas, such as conducting statistical analyses, finding new ideas, and writing in English. Engaging in a detailed examination of ethics committee rules, expanding biostatistics education, increasing the number of institutions providing research funding, and increasing the number of endodontics journals can increase the enthusiasm of endodontics researchers to publish papers.

BACKGROUND/AIMS: As epilepsy is a complex disease group, it is difficult to diagnose and classify. Oxidative stress plays a vital role in the pathogenesis of epilepsy. This study investigated the total oxidant/antioxidant status levels in patients with focal onset and generalized onset seizures. The results we obtained may help find the etiological cause in patients with seizure complaints and may guide their treatment. In addition, knowing the seizure type of the patient can give an idea about the prognosis of their disease.MATERIALS AND METHODS: The total number of patients included in this prospective study was 58. There were also 57 people in a control group. The patients were classified according to their type of seizure: focal or generalized onset. The serum oxidative stress index (OSI) and total oxidant/antioxidant status values of all patients and control group members were measured. The patients (focal/generalized groups) and control group members were compared.RESULTS: This prospective study was completed with 58 eligible patients who met the inclusion criteria. There were 57 people in the control group. Total oxidant status (TOS) and OSI levels were higher in the seizure groups compared to the control group (p

Infantile hemangiomas are oneof the most common benign vascular tumors in infants and children. Because hemangiomas can resolve spontaneously, they usually do not require specific treatment unless the proliferation interferes with normal function or causes interference with the function of essential vital organs. There are severaltypes of therapy, but in recent decades the use of propranolol has become more common due to its excellent effectiveness. The purpose of this paper is to analyze different pharmaceutical formulations of propranolol in the treatment of infantile hemangioma, including technological differences of the oral and topical pharmaceutical dosage forms of propranolol. The European Medicines Agency (EMA) has approved the commercially available oral propranolol therapy in the countries of the European Union, but thisis not yet happened in our country. Recommendations to follow and use the protocols for the oral application of propranolol in the treatment of this disease are difficult due to the fact that this drug formulation is not registered in our country and patients are forced to obtain it from countries where it is registered. The use of syrup as an oral form of therapy has been clinically proven and has a high percentage of efficiency in infantile hemangioma, but side effectssuch as sleep disturbance, bronchospasm, hypoglycemia, hypotension. The goal of this publication is to propose the most appropriate topical formulation of propranolol for external use in infantile hemangioma through a review of relevant published data on the use of various pharmaceutical formulations of propranolol in clinical studies and documents from the European Medicines Agency,In this paper, we used compilation and comparison methods, as most useful for a high-quality critical evaluation of the literature regarding problematic topics, in our case the pharmaceutical formulation of propranolol, the effect of clinical treatment and the required legislation, and which have the potential to promote clearer, shared understandings and accelerate advances in the research. Our results were focused on obtained and published data related to pharmaceutical-technological aspects of production of topical formulations and the effect of clinical application, especially when it is necessary to define exactly the amount of the released active compoundfrom the topical form (cream, ointment or gel) and its absorption through the skin.Topical form of propranolol avoids the side effects of oral administrated propranolol, can help maintain a high level of active ingredient in a local or focal region, and has an easy way of administration.The obtained research data showed that the topical application and penetration of propranolol through the skin is good and has a lower and controlled systemic absorption. To achieve this, the choice of the formulation andthe excipients used are particularly important. Lipophilic formulations have limited release and penetration of propranolol. The best results are achieved by using a hydrophilic cream.After the research done, we can conclude that the production of topical formulations containing specific active components with a strong systemic effect, such as propranolol, can be carried out in galenic laboratories or hospital pharmacies. For this, already existing validated equipment and excipients that are readily available can be used. We believe that the use of topical pharmaceutical forms for local application, even in children such as the case of propranolol in infantile hemangioma, is justified, especially to the fact that so far no side effects have been registered even after long-term therapy

The goal of clinical practice education is to develop the ability to apply theoretical knowledge in a clinical setting and to foster growth as a professional healthcare provider. One effective method of achieving this is through the utilization of Standardized Patients (SP) in education, which familiarizes students with real patient interviews and allows educators to assess their clinical performance skills. However, SP education faces challenges such as the cost of hiring actors and the shortage of professional educators to train them. In this paper, we aim to alleviate these issues by utilizing deep learning models to replace the actors. We employ the Conformer model for the implementation of the AI patient, and we develop a Korean SP scenario data generator to collect data for training responses to diagnostic questions. Our Korean SP scenario data generator is devised to generate SP scenarios based on the provided patient information, using pre-prepared questions and answers. In the AI patient training process, two types of data are employed: common data and personalized data. The common data are employed to develop natural general conversation skills, while personalized data, from the SP scenario, are utilized to learn specific clinical information relevant to a patient’s role. Based on these data, to evaluate the learning efficiency of the Conformer structure, a comparison was conducted with the Transformer using the BLEU score and WER as evaluation metrics. Experimental results showed that the Conformer-based model demonstrated a 3.92% and 6.74% improvement in BLEU and WER performance compared to the Transformer-based model, respectively. The dental AI patient for SP simulation presented in this paper has the potential to be applied to other medical and nursing fields, provided that additional data collection processes are conducted.

Two wheeled Self balancing robots have become more popular in recent times and used in many applications, commonly used in transportation as these balancing robots are faster and apparently stable. Balancing is achieved by using controllers tuned for the system. Inverted pendulum principle is used in these robots. This paper proposes the use of two control methods, namely Proportional-Integral-Derivative (PID) and Extended PID (EPID), for maintaining the balance of two-wheeled and self-balancing robots, even when slightly tilted, thus preventing them from falling. PID control theory generally depends up on transfer functions, this paper extends the theory using EPID. EPID provides a new perspective on the working principle of PID control and its relationship with other control theories, such as tracking control and disturbance observer. This approach is illustrated using the fundamental principle of inverted pendulum technology. The key advantage of these robots over other mobile robots is their increased stability due to zero turning radius, which allows for smoother rotations during changes in direction.

Laboratory methods used for investigation of immune response often involve collection of whole blood and analysis of different biomarkers in blood components or generated from pathogen stimulation of whole blood or peripheral blood mononuclear cells (PBMC). Methods used to measure biomarkers are for example enzyme-linked immunosorbent assay (ELISA) which measures one biomarker at a time or multiplex assays for example x-unknown, multi-analyte profiling (xMAP) by Luminex or proximity extension assay (PEA), which can measure up to just over 3000 biomarkers at a time. Analysis of one biomarker at a time are time consuming, costly, and dependent of a large sample size to enable repeated measurements of different analytes. Therefore, multiplex assays that are time saving, more cost effective and measures multiple bi-omarkers at once in a small sample can be applied. The aim of this thesis was to evaluate multiplex laboratory methods for investigation of the immunological orchestra in response to Borrelia infection and influenza immunisation and if possible, further characterize individuals with different clinical outcomes or serological response, respectively. In our studies (paper I-III) we included 1113 blood donors of which 66 were found to previously have had a subclinical borreliosis (defined as presence of Borrelia-specific antibodies without recall of previous Lyme borreliosis), of the 66 individuals 60 were available for participation. We also included 22 patients previously diagnosed with Lyme neuroborreliosis (LNB). In paper IV we included in total 73 individuals consisting of healthcare workers and patients attending seasonal influenza vaccination. We applied whole blood, PBMC and plasma stimulations and measured a range of cytokines, chemokines and complement factors with ELISA, nephelometry, xMAP and PEA. Our results show that subclinical Lyme borreliosis (SB) individuals display the following pattern, low age, male sex, low amount of secreted interleukin (IL)-17, CCL20 and higher secretion of IL-10 by PBMCs stimulated three days with Borrelia garinii compared to patients with previous Lyme neuroborreliosis (LNB). The subclinical individuals also show higher activation of the complement system in response to Borrelia afzelii. We performed multiplex analysis of complement factors in attempt to further characterize our SB individuals and LNB patient but found the results to deviate largely from reference values retrieved with other standardized methods. This highlights the importance of critical review of generated results from all form of assays. To investigate immune responses after influenza immunisation and further characterize serological responders and nonresponders we included measurement of influenza-specific antibodies and total immunoglobulins (Ig) in blood serum, influenza-specific mucosal IgA (nasal-swabs) and cell-mediated immune response in supernatants from PBMCs stimulated with influenza vaccine using PEA. We found the serological responders to be characterised by lower levels of total IgM, Granzyme B (GZMB) and IL-12 together with higher levels of CXCL13 compared with nonresponders. To conclude, xMAP and PEA are two valuable methods that can be applied together with multivariate statistical methods in the investigation of both innate and adaptive immunity characteristics and association to clinical outcome or serological response after Borrelia infection and influenza immunisation, respectively. Laboratoriemetoder som används för att undersöka immunsvar omfattar bland annat insamling av blod och analys av immunologiska markörer så som exempelvis cytokiner, kemokiner och komplementfaktorer i olika blodkomponenter eller genererade från patogenstimulering av helblod eller från perifert blod, isolerade mononukleära celler (PBMC). Metoder som tillämpas för mätning av cytokiner, kemokiner och komplementfaktorer är bland annat enzyme-linked immunosorbent assay (ELISA), som mäter en markör i taget eller multiplexa analyser som mäter flera markörer (upp till drygt 3000) på en gång exempelvis x-Unknown, multi-analyte profiling (xMAP) och proximity extension assay PEA. Att analysera en markör i taget är tidskrävande, kostsamt och beroende av stor mängd prov för att möjliggöra upprepade mätningar av andra markörer. Därför kan multiplexa analyser tillämpas för att genomföra mätning av flera analyter i en mindre mängd prov och mer tids- och kostnadseffektivt. Syftet med denna avhandling var att tillämpa multiplexa laboratoriemetoder för undersökning av den immunologiska orkesterns svar vid Borreliainfektion och influensavaccination och om möjligt karaktärisera individer som haft olika kliniska symtom respektive antikroppssvar därav. I våra Borrelia studier inkluderades 1113 blodgivare, av vilka vi kunde identifiera 66 individer som haft en subklinisk borrelios (definierad som närvaro av Borrelia-specifika antikroppar, men utan minne av tidigare Borreliainfektion). Av de 66 subkliniska individerna var 60 tillgängliga för vidare studier. Vi inkluderade även 22 patienter som tidigare diagnostiserats med neuroborrelios (LNB). I vår influensavaccinationsstudie inkluderades totalt 73 individer bestående av sjukvårdspersonal och patienter som vaccinerades mot säsongsinfluensa. På våra insamlade prover från studiedeltagarna utfördes sedan stimuleringar av helblod, plasma och PBMC med bland annat borreliabakterier och influensavaccin. Vi analyserade sedan mängden av ett eller flera cytokiner, kemokiner eller komplementfaktorer med ELISA, xMAP och PEA. Våra resultat visade att individer som haft en subklinisk borrelios har följande mönster, de är unga män med låg mängd interleukin (IL)-17, CCL20 och högre mängd IL-10 utsöndrat av PBMC stimulerade med Borrelia garinii i tre dagar och i jämförelse med patienter med tidigare LNB. Subkliniska individer har även en högre komplementaktivering än LNB patienter i respons till Borrelia afzelii. För att vidare karaktärisera våra individer med tidigare subklinisk borrelios och LNB patienter analyserade vi mängden av flera komplementfaktorer med xMAP teknik, men våra resultat var inte överensstämmande med referensvärden uppmätta med andra standardiserade metoder. Dessa resultat belyser vikten av att alltid utföra en rimlighetsbedömning av sina analysresultat. För att undersöka immunsvar efter influensavaccination och vidare karaktärisera individer som får ett antikroppssvar (responders) efter vaccination jämfört med de som inte får ett antikroppssvar (nonresponders) så utfördes mätning av influensa-specifika antikroppar och totala antikroppar (även kallade immunoglobuliner, Ig) i serum, influensaspecifika mukosala (i nässlemhinnan) IgA och cellmedierat immunsvar i ovanlösningar från PBMC stimulerade med influensavaccin med hjälp av PEA. Vi fann att responders karaktäriseras av lägre nivå av total IgM, granzym B och IL-12 samt högre nivå av CXCL13 jämfört med nonresponders. Vi kan konkludera att xMAP och PEA tillsammans med multivariat statistiska metoder är bra metoder för att undersöka immunsvar med ett vidare perspektiv av den immunologiska orkesterns sammansättning efter Borreliainfektion eller influensavaccination.

Removal of impacted permanent third molars is considered to be one of the most common and routine oral surgical procedures. This intervention is usually performed in the classical way with the use of rotatory instruments and burs. As an alternative to this classical approach, piezosurgery can be used, which is an osteotomy technique based on ultrasonic vibrations. The crucial advantage of piezosurgery is that it is inert to soft tissues. The aim of this study was to compare piezosurgery with the rotatory osteotomy technique, with particular reference to the time required to perform the intervention and the intensity of postoperative sequelae: pain, swelling, and trismus. This paper summarizes published experiences and knowledge of piezosurgery, with special regard to the extraction of mandibular third molars. For the purposes of this research, an automatic detailed search was performed on the electronic database PubMed for the period 2012-2022. Keywords used in the search were: piezosurgery, impacted third molars. The initial filtration resulted in 47 scientific papers, 17 of which met the selection criteria. Of particular interest were papers such as Meta-analyzes and systematic reviews. A review of the literature indicates that although patients undergoing piezosurgery required longer operating times, they had less postoperative pain, swelling, and trismus. Keywords: impacted molar, piezosurgery.

The goal of this review paper is to bring coherence and integration to the broad field of Cognitive behavioral therapy (CBT) psychotherapy practice based on the constraints of neurosciences. This goal was articulated over 100 years ago but is one that can now be realistically envisioned due to advances in neuroscientific knowledge. In recent years, interdisciplinary research in the field of neurosciences has expanded our knowledge about neurobiological correlates of mental processes and changes occurring in the brain due to therapeutic interventions. Although CBT is an established and efficient treatment for a variety of common mental disorders, a considerable number of patients do not respond to treatment or relapse after successful CBT (Månsson, Lueken &Frick, 2020). Based on the findings and different approaches we will present how neurosciences can offer novel perspectives to better understand: (a) the neurobiological underpinnings of CBT, especially neuroplasticity, (b) cognitive activity contributes to dysfunctional behavior and emotional experience through focusing, selective perception, memory and recall, and characteristic cognitive distortion; on a neurobiological level, there is a relationship between top-down and bottom-up regulation of unpleasant emotional states, (c) how we can enrich CBT with neuroscience-informed techniques (augmentation of CBT), (d) neurosciences and enduring changes (implications for CBT), implications why some patients may respond better to CBT than others, thus paving the way for more personalized and effective treatments. The goal of our paper is also to delineate the mechanisms involved in optimizing the degree and duration of clinical improvement. By translating psychotherapy interventions into brain-based processes, delineating different memory processes and the mechanisms of change associated with each, and understanding the role of emotion in effecting change in interaction with these memory mechanisms, the potential exists to develop a new taxonomy of clinical interventions based on what problems are being targeted, how long they have been in place, how intractable they are, and whether an important goal is to achieve enduring change (Nadel & Lane, 2020). We will introduce some key topics and describe a selection of findings from CBT-related research using tools from neuroscience, with the hope that this will provide clinicians and clinical researchers with a brief and comprehensible overview of the field. Key words: CBT; Neurosciences; Neuroimaging; Integration; Personalized therapy

Introdução e objetivos - O ato da observação é uma competência fundamental em neurologia clínica. O Professor William Campbell descreve no seu artigo clássico o ato de "Augenblickdiagnose" ("diagnóstico num piscar de olhos"), que consiste na identificação de pistas de alto valor semiológico como base para se considerar uma hipótese diagnóstica. O nosso trabalho pretende fornecer vinhetas clínicas adicionais com foco em entidades nosológicas não exploradas no trabalho original. Métodos - Foi realizada uma revisão não-sistemática da literatura e procedeu-se à redação de vinhetas baseadas na experiência clínica dos autores. Resultados - Descrevemos várias vinhetas clínicas e apresentamo-las em diferentes tabelas, alocando-as às principais áreas neurologia. Discussão - Várias vinhetas clínicas são apresentadas. São também discutidos possíveis vieses cognitivos. Conclusão - A prática clínica em neurologia centra-se na realização de um exame neurológico cuidado e na recolha de uma história clínica adequada. As vinhetas clínicas podem ser um recurso educacional muito relevante. Introduction and objectives - The act of observation is a core skill in clinical practice, particularly in the field of neurology. Professor William Campbell explored the concept of Augenblickdiagnose ("diagnosis in the blink of an eye") in his seminal paper, through the narration of clinical vignettes with high-value information supposed to prompt an immediate diagnosis. Our work aims to update Professor William Campbell's seminal paper, by providing new clinical vignettes. Methods - We performed a non-systematic review of the literature and wrote clinical vignettes based on the clinical experience of the authors. Results - We described several clinical vignettes and presented them in separate tables allocated to major fields in neurology. Discussion - Several clinical vignettes regarding classic presentations of neurological conditions are presented. Cognitive biases of this practice are also discussed. Conclusion - The staple of neurology practice resides in a carefully conducted neurological examination and history taking. Clinical vignettes may serve as powerful educational tools.

Objetivo: A Perturbação de Ingestão Alimentar Evitante/Restritiva (sigla em inglês ARFID) foi introduzida como um novo diagnóstico no DSM-5 para descrever um grupo de indivíduos que têm comportamentos alimentares evitativos e restritivos que, ao contrário da Anorexia Nervosa (AN), não são impulsionados pelas preocupações com o peso e a forma. O objetivo desta revisão foi explorar os estudos que compararam diretamente grupos de indivíduos com ARFID e indivíduos com AN, destacando semelhanças e diferenças entre as duas patologias, de forma a compreender melhor a ARFID, bem como identificar as principais lacunas no conhecimento da mesma. Método: Foi realizada uma revisão sistemática de escopo de artigos na Scopus, PubMed e Web of Science até outubro de 2021, seguindo as diretrizes PRISMA-ScR. Os estudos foram incluídos se estivessem escritos em inglês e se comparassem especificamente indivíduos com ARFID e indivíduos com AN. Resultados: Foram identificadas 28 publicações originais. Os achados dessas publicações foram sintetizados e categorizados em sete áreas temáticas: características sociodemográficas, psicopatologia das perturbações alimentares, comorbilidades psiquiátricas, comorbilidades/complicações médicas, diferenças endocrinológicas, saúde óssea e outcomes clínicos. Embora muitas das características e sintomas da ARFID sejam semelhantes aos encontrados em indivíduos com AN, a evidência atual revela muitas diferenças entre estas duas patologias e apoia a ARFID como uma entidade clínica distinta da AN, embora o conhecimento da ARFID nas várias áreas seja ainda limitado. Discussão: Embora a ARFID e a AN sejam ambas classificadas como perturbações alimentares restritivas, são entidades muito distintas, com diferenças nas características sociodemográficas, sintomas alimentares, comorbilidades e outcomes clínicos. Esta revisão ajuda a melhorar o nosso conhecimento sobre a ARFID e aborda futuros desafios na investigação desta patologia. Objective: Avoidant/restrictive food intake disorder (ARFID) was introduced as a new diagnosis in the DSM-5 to describe a group of individuals who have avoidant and restrictive eating behaviours that are not driven by the weight and shape concerns that typify Anorexia Nervosa (AN). The aim of this review was to explore those studies that have directly compared groups of individuals with ARFID and AN, highlighting similarities and differences between the two conditions, to enhance our understanding of ARFID, as well as identify key gaps in knowledge. Method: A systematic scoping review of papers in Scopus, PubMed and Web of Science was undertaken to October 2021, following PRISMA-ScR guidelines. Studies were included if they were in English and empirical research papers specifically comparing individuals with ARFID and AN. Results: Twenty-eight original research publications were identified. This literature was synthesised and categorised into seven subject areas: sociodemographic characteristics, eating-disorder psychopathology, psychiatric comorbidities, medical comorbidities/complications, endocrine differences, bone health and clinical outcomes. While many of the ARFID characteristics and symptoms are similar to those found in individuals experiencing AN, the current evidence base reveals many differences between these conditions and supports ARFID as a distinct clinical entity, although there is a limited understanding in all areas. Discussion: Although ARFID and AN are both classified as restrictive eating disorders, they are very distinct entities with differences in sociodemographic characteristics, eating symptoms, comorbidities, and clinical outcomes. This review helps to improve our knowledge about ARFID and addresses future research challenges.

deep brain stimulation (DBS) is an established method for symptom control in movement disorders such as Parkinson’s disease (PD) and essential tremor (ET). The treatment consists in delivering electrical stimulation in the deep brain via multi-contact electrodes. The potential for improving quality of life is important and the precision of the electrode implantation is crucial. Despite the success of the therapy, mechanisms of action of DBS are still an intense topic of study. One promising approach is to analyze the effect of stimulation relative to the anatomy. In the clinical process, the effect of stimulation on the symptoms is evaluated at different stages, sometimes during surgery (intraoperative) and systematically in the months following implantation (postoperative). This data can be combined with magnetic resonance imaging (MRI) acquired as part of the clinical routine for individuals or groups of patients to create probabilistic stimulation maps (PSMs). The work in this thesis aimed at developing image and data processing workflows to analyze and visualize DBS outcome in the ventro-intermediate nucleus of the thalamus (Vim) and the Zona Incerta (Zi) which are the two typical ET targets. This was done first in a patient-specific manner, and then at a group level using data collected intra- and postoperatively. Computer electrical field modeling was used to estimate the extent of stimulation within brain tissue and to compare intraoperative and postoperative stimulation (Paper I). The simulation method was then applied to clinical data, combining quantitative tremor assessment collected using acceleration sensors during intraoperative testing in the Vim, to create patient-specific stimulation maps based on high resolution objective data (Paper II). Stimulation maps constitute a partial answer to the aim by providing a visual summary of individual patients’ stimulation tests that can be useful in the clinic. In order to summarize several patients’ data, neuroimaging workflows were developed, and a range of non-linear image registration tools were evaluated to create group-specific anatomical templates from MRI using data from 19 patients (Paper III). The normalization workflow was improved and the settings optimized, resulting in the creation of an anatomical atlas defining the outline of 58 structures of the deep brain (Paper IV). The normalization method was transferred to a second group of 77 patients with postoperative stimulation tests in Zi, and combined with patient specific electric field modeling to create PSMs. The influence of different methodological choices such as input data type and voxel clustering method on the resulting maps were investigated (Paper V). The deep brain atlas from the first group was then combined with electric field simulations and the acceleration-sensor-based quantitative tremor assessment. A stimulation atlas based on intraoperative test data in Vim was created (Paper VI) to evaluate of the potential of intraoperative test stimulation for PSM creation. In conclusion, reproducible pipelines for the generation of group-specific brain templates and high precision PSMs were developed and applied to two different patient groups. The template created for one group resulted in a deep brain atlas defining 58 anatomical structures. The PSMs created for both groups combine group-specific MRI templates, patient-specific electric field simulation and symptom assessment for two common DBS targets that are challenging to locate. The PSMs have the potential to improve the understanding of the mechanisms of action, support clinical planning and aid follow-up by providing visualizations of the therapeutic effect of stimulation in relation to anatomy. In the future, the pipeline will be applied to more patients and diseases. The resulting PSMs will be integrated in a visualization tool for intuitive data exploration and used to predict programming settings. Djup hjärnstimulering (DBS) är en etablerad metod för behandling av symtom vid rörelsesjukdomar såsom Parkinsons sjukdom (PD) och essentiell tremor (ET). Behandlingen består av elektrisk stimulering av djupa hjärnstrukturer via små elektroder. Stimuleringens effekt på patientens symtom utvärderas kliniskt, ibland under operationen (intraoperativt) och systematiskt under månaderna efter implantationen (postoperativt). Data som samlas in vid dessa utvärderingar kan kombineras med magnetresonans (MR) bilder och simuleringar av elektriska fält runt DBS elektroderna. Detta kan utföras för enskilda patienter eller grupper av patienter, det senare för att skapa statistiska stimuleringskartor. Arbetet i denna avhandling syftar till att utveckla arbetsflöden för bild- och databehandling för att analysera och visualisera DBS-resultat. Två typiska målstrukturer för implantering av DBS elektroder har studerats, ventro-intermediate kärnan (Vim) i talamus och zona incerta (Zi). Modellering och simulering av elektriska fält användes för att jämföra storleken av stimuleringsvolymen baserad på intraoperativ testelektrod och postoperativ DBS elektrod (Papper I). Simuleringsmetoden tillämpades sedan på kliniska data och kombinerades med kvantitativ förbättring av tremor med hjälp av accelerometrar under intraoperativ testning i Vim, och patientspecifika stimuleringskartor skapades (Papper II). För att sammanfatta flera patienters data utvecklades ett arbetsflöde för normalisering av MR bilder. En rad verktyg för icke-linjär bildregistrering utvärderades för att skapa gruppspecifika anatomiska mallar från MR bilder med hjälp av data från 19 patienter (Papper III). Arbetsflödet för normalisering förbättrades och inställningarna optimerades, vilket resulterade i en anatomisk atlas som definierar konturerna av 58 strukturer i den djupa hjärnan (Papper IV). Normaliseringsmetoden överfördes till en större patientgrupp på 77 patienter med postoperativa stimuleringstester i Zi och kombinerades med patientspecifik modellering av elektriska fält för att skapa stimuleringskartor. Påverkan av metodologiska val, t.ex. typ av indata och klustermetod, på de resulterande kartorna undersöktes i Papper V. Den anatomiska atlasen från Papper III kombinerades sedan med simuleringar av elektriska fält och den kvantitativa tremorförbättningen. Detta resulterade i en stimuleringskarta baserad på intraoperativa testdata i Vim (Papper VI). Sammanfattningsvis utvecklades arbetsflöden för generering av stimuleringskartor för två patientgrupper med DBS implantat. Stimuleringskartorna kombinerar MR-bilder, patientspecifik simulering av elektriska fält och symtombedömning för två vanliga DBS-mål som är svåra att lokalisera. Stimuleringskartorna har potential att förbättra förståelsen av DBS mekanismerna, stödja klinisk planering och underlätta uppföljning genom att visualisera stimuleringens terapeutiska effekt i förhållande till anatomin. Funding agencies: This thesis was supported financially by the University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences, via the strategic PhD grant, the Swedish foundation for strategic research (SSFBD15-0032) and the Swedish Research Council (VR2016-03564).

ObjectiveThe primary aim of this current systematic review and meta-analysis was to evaluate the potential microbiological effect of probiotics on the implant microbiota. The secondary aim was to evaluate if probiotics have any effect as an adjunct to non-surgical peri-implant treatment in reducing peri-implant mucositis and peri-implantitis clinical parameters—bleeding on probing, modified Gingival Index, and pocket depth.MethodsThe research focus questions were constructed in accordance with the Participants, Intervention, Comparison, and Outcomes (PICO) criteria, and a PROSPERO protocol was registered. A comprehensive systematic search in MEDLINE via the PubMed, Scopus, and Web of Science Core Collection databases was conducted. Two independent reviewers screened the reports based on the PICO criteria—inclusion and exclusion criteria.ResultsIn total, 467 records were identified, and ultimately, 7 papers were included: 3 papers in the qualitative synthesis of microbiological effect and 4 in the meta-analysis synthesis on pocket depth. The data synthesis showed that probiotics had no detectable effect on the implant microflora, and in the following data synthesis, no clinical peri-implantitis variable showed a significantly beneficial effect from probiotics in the test group compared to the control group.ConclusionWithin the limitations of this review, the oral implant microflora is not affected by probiotics nor do probiotics add any effect to the conventional non-surgical treatment of peri-implant mucositis and peri-implantitis.

Introduction Pure Neural Leprosy (PNL) is a rare clinical form of leprosy in which patients do not present with the classical skin lesions but have a high burden of the disability associated with the disease. Clinical characteristics and follow up of patients in PNL are still poorly described in the literature. Objective This paper aims to describe the clinical, electrophysiological and histopathological characteristics of PNL patients, as well as their evolution after multidrug therapy (MDT). Methods Fifty-two PNL patients were selected. Clinical, nerve conduction studies (NCS), histopathological and anti-PGL-1serology were evaluated. Patients were also assessed monthly during the MDT. At the end of the MDT, all of the patients had a new neurological examination and 44 were submitted to another NCS. Results Paresthesia was the complaint most frequently reported by patients, and in the neurological examination the most common pattern observed was impairment in sensory and motor examination and a mononeuropathy multiplex. Painful nerve enlargement, a classical symptom of leprosy neuropathy, was observed in a minority of patients and in the motor NCS axonal injuries, alone or in combination with demyelinating features, were the most commonly observed. 88% of the patients did not present any leprosy reaction during MDT. There was no statistically significant difference between the neurological examinations, nor the NCS pattern, performed before and after the MDT. Discussion The classical hallmarks of leprosy neuropathy are not always present in PNL making the diagnosis even more challenging. Nerve biopsy is an important tool for PNL diagnosis as it may guide therapeutic decisions. This paper highlights unique characteristics of PNL in the spectrum of leprosy in an attempt to facilitate the diagnosis and management of these patients., Author summary Neuropathy is responsible for most of the disability associated with leprosy disease. The pure neural leprosy (PNL), in spite of being a rare clinical presentation of that, has some singular characteristics that are still poorly studied. In this study, we selected 52 patients at the diagnosis to describe their clinical, neurophysiological and histopathological presentation patterns as well as their evolution during the multidrug therapy (MDT). We confirmed that sensitive symptoms were the most commonly described by PNL patients but neural pain is rare. Also confirmed that mononeuropathy mutiplex was the most common pattern observed at neurological examination and at the nerve conduction studies at the moment of the diagnosis. However we showed that painful nerve enlargement other cardinal signs of leprosy, besides the skin lesions, is not common in this group of patients, There was no statistically significant difference between the neurological examination and NCS performed before and after the MDT.During the MDT88.4% of the patients did not have any leprosy reaction. This may suggest that that MDT was effective in stopping disease progression. Our results highlight the difficulties in the diagnosis of PNL and the progression following MDT in an attempt to prevent further disability in PNL patients.

The aim of this article is to assess both the economic and social value of balneotherapy and spa tourism, being the first paper in carrying out this analysis. The study has been conducted in Maresme, a region of Catalonia, Spain. On the one hand, an Input-Output (IO) model with a Social Accounting Matrix (SAM) has been carried out to assess the economic value. On the other hand, a Cost-Benefit Analysis (CBA) has been used to monetise the social value in this region, taking into account, among other concepts, direct and indirect health profits, given that balneotherapy helps to alleviate various diseases. The results show that whereas the economic multiplier is 1.529 considering the direct and indirect effects and 1.712 taking into account also the induced effects, which are similar to health and medical tourism multipliers, social value generates additional positive value, given that the cost-benefit ratio is 1.858. The theoretical implications of the paper as well as the findings’ implications for policy so as to encourage investments in spa tourism are discussed.

Background During the Coronavirus Disease 2019 (COVID-19) pandemic, the number of consultations and diagnoses in primary care and referrals to specialist care declined substantially compared to prepandemic levels. Beyond deferral of elective non-COVID-19 care by healthcare providers, it is unclear to what extent healthcare avoidance by community-dwelling individuals contributed to this decline in routine healthcare utilisation. Moreover, it is uncertain which specific symptoms were left unheeded by patients and which determinants predispose to healthcare avoidance in the general population. In this cross-sectional study, we assessed prevalence of healthcare avoidance during the pandemic from a patient perspective, including symptoms that were left unheeded, as well as determinants of healthcare avoidance. Methods and findings On April 20, 2020, a paper COVID-19 survey addressing healthcare utilisation, socioeconomic factors, mental and physical health, medication use, and COVID-19–specific symptoms was sent out to 8,732 participants from the population-based Rotterdam Study (response rate 73%). All questionnaires were returned before July 10, 2020. By hand, prevalence of healthcare avoidance was subsequently verified through free text analysis of medical records of general practitioners. Odds ratios (ORs) for avoidance were determined using logistic regression models, adjusted for age, sex, and history of chronic diseases. We found that 1,142 of 5,656 included participants (20.2%) reported having avoided healthcare. Of those, 414 participants (36.3%) reported symptoms that potentially warranted urgent evaluation, including limb weakness (13.6%), palpitations (10.8%), and chest pain (10.2%). Determinants related to avoidance were older age (adjusted OR 1.14 [95% confidence interval (CI) 1.08 to 1.21]), female sex (1.58 [1.38 to 1.82]), low educational level (primary education versus higher vocational/university 1.21 [1.01 to 1.46), poor self-appreciated health (per level decrease 2.00 [1.80 to 2.22]), unemployment (versus employed 2.29 [1.54 to 3.39]), smoking (1.34 [1.08 to 1.65]), concern about contracting COVID-19 (per level increase 1.28 [1.19 to 1.38]) and symptoms of depression (per point increase 1.13 [1.11 to 1.14]) and anxiety (per point increase 1.16 [1.14 to 1.18]). Study limitations included uncertainty about (perceived) severity of the reported symptoms and potentially limited generalisability given the ethnically homogeneous study population. Conclusions In this population-based cross-sectional study, 1 in 5 individuals avoided healthcare during lockdown in the COVID-19 pandemic, often for potentially urgent symptoms. Healthcare avoidance was strongly associated with female sex, fragile self-appreciated health, and high levels of depression and anxiety. These results emphasise the need for targeted public education urging these vulnerable patients to timely seek medical care for their symptoms to mitigate major health consequences., Marije J. Splinter and colleagues assess the prevalence of healthcare avoidance during the COIVD-19 pandemic and investigate related determinants, Author summary Why was this study done? ➢ During the Coronavirus Disease 2019 (COVID-19) pandemic, consultation rates in both primary and specialist care declined compared to prepandemic levels, which can partially be attributed to the postponement or cancellation of elective and nonurgent medical care. ➢ It is unclear to what extent these declines in consultation rates could be related to healthcare avoidance by patients in the general population. ➢ To evaluate the collateral health damage of the COVID-19 pandemic, it is important to not only assess the prevalence of healthcare avoidance, but also for what symptoms healthcare was avoided and which determinants are associated with this behaviour. What did the researchers do and find? ➢ We sent out a paper questionnaire to 8,732 participants of the population-based Rotterdam Study containing several COVID-19–related subjects, such as healthcare utilisation, work status, mental and physical health, and concerns about contracting COVID-19. ➢ About 6,241 participants (73%) returned the questionnaire, of whom 5,656 participants (90.6%) were included in our analyses. We found that 1,142 of them (20.2%) avoided healthcare during the COVID-19 pandemic, often for symptoms that might have needed urgent medical evaluation, such as limb weakness (13.6%), palpitations (10.8%), and chest pain (10.2%). ➢ Determinants that were most strongly associated with healthcare avoidance were female sex, poor self-appreciated health, and high levels of depression and anxiety. What do these findings mean? ➢ The results of this population-based study suggest that healthcare avoidance contributed to the decline in consultation rates during the COVID-19 pandemic. Importantly, our findings suggest that this behaviour may be associated with certain vulnerable groups within the population. ➢ These findings should be interpreted in light of the limitations of this study, which include that the actual severity of the symptoms that were reported by participants is unknown, since they were not medically evaluated when they experienced these symptoms. ➢ The findings of this study can be used to develop policy interventions targeted to vulnerable individuals who may be more likely to exhibit healthcare avoiding behaviours.

Objective: The proliferation and growing demands of genetic testing are anticipated to revolutionise medical practice. As gatekeepers of healthcare systems, general practitioners (GPs) are expected to play a critical role in the provision of clinical genetic services. This paper aims to review existing literature on GPs' experience, attitudes and needs towards clinical genetic services. Design: A systematic mixed studies review of papers published between 2010 and 2022. Eligibility criteria: The inclusion criterion was peer-reviewed articles in English and related to GPs' experience, views and needs on any genetic testing. Information sources: The PubMed, PsycINFO, Cochrane, EMBASE databases were searched using Mesh terms, Boolean and wildcards combinations to identify peer-reviewed articles published from 2010 to 2022. Study quality was assessed using Mixed Methods Appraisal Tool. Only articles that fulfilled the inclusion criteria were selected. A thematic meta-synthesis was conducted on the final sample of selected articles to identify key themes. Results: A total of 62 articles were included in the review. Uncertainty over GPs' role in providing genetic services were attributed by the lack of confidence and time constraints and rarity of cases may further exacerbate their reluctance to shoulder an expanded role in clinical genetics. Although educational interventions were found to increasing GPs' knowledge and confidence to carry out genetic tasks, varied interest on genetic testing and preference for a shared care model with other genetic health professionals have resulted in minimal translation to clinical adoption. Conclusion: This review highlights the need for deeper exploration of GPs' varied experience and attitudes towards clinical genetic services to better facilitate targeted intervention in the adoption of clinical genetics. Ministry of Health (MOH) Nanyang Technological University National Medical Research Council (NMRC) Published version This research is supported by the Singapore Ministry of Health’s National Medical Research Council under its Clinician Scientist Award (MOH-¬000654) as well as the Centre for Primary Health Care Research & Innovation, Lee Kong Chian School of Medicine Seedcorn grant (L0483103 NHG--CPHCRI).

Biosocial Medicine, with its emphasis on the full integration of the person's biology and biography, proposes a strategy for clinical research and the practice of medicine that is transformative for the care of individual patients. In this paper, we argue that Biology is one component of what makes a person unique, but it does not do so alone. Biography, the lived experience of the person, integrates with biology to create a unique signature for each individual and is the foundational concept on which Biosocial Medicine is based. Biosocial Medicine starts with the premise that the individual patient is the focus of clinical care, and that average results for “ideal” patients in population level research cannot substitute for the “real” patient for whom clinical decisions are needed. The paper begins with a description of the case-based method of clinical reasoning, considers the strengths and limitations of Randomized Controlled Trials and Evidence Based Medicine, reviews the increasing focus on precision medicine and then explores the neglected role of biography as part of a new approach to the tailored care of patients. After a review of the analytical challenges in Biosocial Medicine, the paper concludes by linking the physician's commitment to understanding the patient's biography as a critical element in developing trust with the patient.

Background Early reports on the pandemic nature of coronavirus disease 2019 (COVID-19) directed the nephrology community to develop infection prevention and control (IPC) guidance. We aimed to make an inventory of strategies that dialysis centres followed to prevent infection with COVID-19 in the first pandemic wave. Methods We analyzed IPC measures taken by hemodialysis centres treating patients presenting with COVID-19 between 1 March 2020 and 31 July 2020 and that completed the European Renal Association COVID-19 Database centre questionnaire. Additionally, we made an inventory of guidelines published in European countries to prevent spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in dialysis centres. Results Data from 73 dialysis units located in and bordering Europe were analyzed. All participating centres implemented IPC measures to mitigate the impact of SARS-CoV-2 during the first pandemic wave. Measures mentioned most often included triage with questions before entering the dialysis ward, measuring body temperature, hand disinfection, masking for all patients and staff, and personal protective equipment for staff members. These measures were also recommended in most of the 14 guidelines that were identified in the inventory of national guidelines and were also scored as being among the most important measures by the authors of this paper. Heterogeneity existed between centres and national guidelines regarding the minimal distance between dialysis chairs and recommendations regarding isolation and cohorting. Conclusions Although variation existed, measures to prevent transmission of SARS-CoV-2 were relatively similar across centres and national guidelines. Further research is needed to assess causal relationships between measures taken and spread of SARS-CoV-2.

Enquadramento: Chemsex é um neologismo combinando 'chemical' e 'sex'. Trata-se de um subtipo de Uso Sexualizado de Drogas (USD), especialmente praticado entre Homens Gays e Bissexuais que têm Sexo com Homens (HGBSH). USD está associado a sexo que dura por horas ou dias com múltiplos parceiros sexuais, o que aumenta a prevalência de infeções sexualmente transmissíveis. As drogas de chemsex mais usadas são agrupáveis em três famílias: metanfetaminas, catinonas sintéticas e ácido γ-hidroxibutírico/ γ-butirolactona. Objetivo: O objetivo deste estudo é identificar e discutir as motivações e razões para a população de HGBSH participar nas experiências de chemsex. Métodos: Uma revisão sistemática baseada em artigos publicados entre 2010 e 2022 foi conduzida de acordo com as orientações do PRISMA. As bases de dados pesquisadas foram PubMed/Medline, Scopus, Google Scholar e PsycINFO. Resultados: A nossa pesquisa identificou 1400 publicações, das quais 23 foram incluídas. Motivações para participar em chemsex foram agregados como se segue: (1) Aprimorar as sensações e desempenho sexuais, (2) Atingir estados mentais hedónicos, (3) Lidar com pensamentos e sentimentos negativos, e (4) motivações sociais. Diferentes métodos de amostragem e formas de perguntar as motivações poderão limitar a validade interna destas conclusões. Conclusões: Ambos os fatores individuais e sociais estão envolvidos na decisão de participar no chemsex. Esta realidade não deverá ser medicalizada, mas o suporte terapêutico deverá providenciar intervenções multidisciplinares, centradas no prazer e com suporte de redução de riscos, especialmente desenhados para esta minoria de HGBSH. Background: Chemsex is a neologism mixing chemical and sex. It is a subtype of Sexualized drug use (SDU), especially practised among Gay and Bisexual Men who have Sex with Men (GBMSM). SDU is associated with sex lasting hours or days with multiple sexual partners which increase prevalence of Sexual Transmitted Infections among this population. The most used chemsex drugs are grouped in three families: methamphetamines, synthetic cathinones and γ-hydroxybutyric acid/ γ-butyrolactone. Aim: This study aims to identify and discuss the motivations and reasons to engage in chemsex experiences in GBMSM population. Methods: A systematic review based on papers published between 2010 and 2022 was conducted according to PRISMA guidelines. Searched data bases were PubMed/Medline, Scopus, Google Scholar and PsycINFO. Results: Our search identified 1400 publications, of which 23 were included. Motivations to engage in chemsex were aggregated as follows: (1) Enhancing sexual sensations and performance, (2) Achieving hedonic mental and emotional states, (3) Tackle negative thoughts and feelings, and (4) Social motivations. Different sample methods and ways of asking motivations may limit internal validity of these conclusions. Conclusions: Both individual and social factors are involved in the decision to engage in chemsex. This reality should not be medicalized, however therapeutic support should provide multidisciplinary, pleasure-centred, harm reducing care interventions, specifically designed to these minority of GBMSM.

A retinopatia diabética (RD) é uma complicação microvascular da diabetes mellitus e é uma das causas mais frequentes de cegueira na população adulta em todo o mundo, particularmente nos países de baixos rendimentos. O diagnóstico e tratamento precoces são primordiais na gestão desta doença e para que, subsequentemente, se obtenha um melhor prognóstico. Além disso, é recomendado pela maioria das guidelines de prática clínica que seja efetuado um rastreio universal da RD entre os doentes diabéticos. Para este efeito, nos últimos anos, têm sido realizados vários estudos para avaliar a capacidade dos modelos de inteligência artificial no âmbito da deteção precoce de RD. Em particular, o uso de modelos de deep learning baseados em redes neurais convolutas, que são treinadas para reconhecer automaticamente padrões patológicos e extrair características de lesão das imagens do fundo da retina, permite a classificação da RD de acordo com as cinco classes da Escala Internacional de Gravidade da Doença de Retinopatia Clínica Diabética e entre RD referenciável ou não referenciável. Esta monografia visa avaliar a precisão dos modelos de deep learning utilizados em estudos recentes na detecção e classificação de RD e o quão bem se comparam com a classificação manual da doença. Para este efeito, concluímos que já existem vários modelos, considerados de última geração, que podem detetar e classificar RD com níveis muito elevados de precisão, sensibilidade e especificidade, superando as capacidades dos profissionais de saúde, com a vantagem de tere, uma reprodutibilidade muito elevada e de poderem funcionar ininterruptamente sem repercussões resultantes em fadiga. Contudo, existem ainda alguns problemas com a falta de interpretabilidade do raciocínio dos modelos e a falta de validação clínica em diferentes contextos. Além disso, os modelos de deep learning necessitam de uma enorme quantidade de dados para serem treinados e existe uma disponibilidade limitada de imagens de fundos da retina com boa qualidade. A este respeito, abordámos também a importância dos métodos de pré-processamento das imagens da retina e das técnicas de data augmentation, a fim de aumentar a quantidade de material por onde os modelos podem ser treinados. Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus and is one of the most frequent causes of blindness in the adult population worldwide, particularly in low-income countries. Early diagnosis and treatment are paramount in the management of this condition and, subsequentially, to ensurea better prognosis. Also, it is recommended by most clinical practice guidelines that there should be a universal screening for DR amongst diabetic patients. For this matter, in recent years, many studies have been conducted to assess the capability of artificial intelligence models for aiding on the early detection of DR. In particular, the use of deep learning models based on convoluted neural networks, which are trained to automatically recognize pathological patterns and extract lesion features from retinal fundus images, allows DR grading according to the five classes of the International Clinical Diabetic Retinopathy Disease Severity Scale and between referable or non-referable DR. This paper aimed to evaluate the accuracy of deep learning networks used in recent studies in detecting and classifying DR and how well they compare to the manual grading of the disease. For this purpose, we concluded that there are already several models, considered to be state-of-the-art, that can detect and grade DR with very high levels of accuracy, sensitivity and specificity, surpassing the capabilities of health care professionals, with the advantage of having a very high reproducibility and being able to operate continuously without experiencing the effects of fatigue. However, there are still some issues with the lack of interpretability of the models' reasoning and the lack of clinical validation in different contexts. Also, the deep learning models need an enormous amount of data to be trained and there is a limited availability of retinal fundus images with good quality. In this regard, we have also addressed the importance of preprocessing methods for the retinal images and data augmentation techniques in order to increase the quantity of material from where the models can be trained.

Objective: Mobile applications have been used frequently in post-operative orthopedic rehabilitation in recent years. However, no systematic review has emphasized the importance of mobile applications in the rehabilitation process after total knee arthroplasty (TKA). This systematic review and meta-analysis aimed to evaluate the effectiveness of mobile application-based rehabilitation practices in patients with TKA. Material and Methods: PubMed, Web-of-Science, Scopus, ScienceDirect and Cochrane databases were searched. The Physiotherapy Evidence Database (PEDro) and the Revised Cochrane risk-of-bias tool randomized trials 2 (RoB2) tools were used to demonstrate the methodological quality and risk of bias. Results: A total of 584 articles were screened. Finally, six papers were included in the systematic review. PEDro scores ranged from 4 to 7 (median: 5.5), indicating fair to good methodological quality. All studies were classified as \"some concerns\" in RoB2. Mobile application-based rehabilitation demonstrated better scores on pain, range of motion (ROM), objective and subjective function, satisfaction and compliance in general. Meta-analysis proved that mobile application-based telerehabilitation demonstrated better results on subjective function (ES:0.57, 95% CI: 0.11–1.02). Conclusion: Compared to conventional rehabilitation, application-based telerehabilitation provides more effective results in function, pain and ROM. Furthermore, mobile application-based rehabilitation should also be considered regarding patient satisfaction and compliance.

Introduction: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic disease causing inflammation in the gut mucosa. The pathogenesis involves alteration in gut microbiota and in the intestinal barrier due to genetic factors, environmental exposure and dysregulation of the immune response. Several environmental risk factors and risk genes have been identified, but still, the pathogenesis is not fully understood. Methods: Included papers are all case-control studies based on previously collected data stored with the biobank in Umeå, Sweden. Cases are individuals that participated in the Northern Sweden Health and Disease Study (NSHDS) at least one year before developing IBD. Information was available for all cases regarding age, time and place for inclusion in NSHDS, height and weight, sex and tobacco use. Part of the cases also had available data from a detailed food-frequency questionnaire. For each available case, controls matched for age, sex and time and place were selected. Analysed factors included tobacco use, with smoking and snuff use analysed separately), cotinine (a metabolite of nicotine), iron status (including ferritin, iron, transferrin and transferrin saturation), B-vitamins and tryptophan metabolites. Results: Smoking was associated with an increased risk of developing IBD both based on questionnaire data and using cotinine as a marker for exposure. Snuff use was not associated with risk for developing IBD. A lower ferritin was associated with an increased risk of developing IBD, whereas no association was seen for other iron status analytes. When analysing iron deficiency based on ferritin and CRP, it was shown that iron deficiency was more common among men before onset of IBD, whereas no difference was seen for women. Active vitamin B6 was lower among cases compared to controls, as well as an index indicating functional B6 deficiency. Kynurenic acid and xanthurenic acid, both tryptophan metabolites with immunomodulatory properties, were lower among cases than controls. For CD only, picolinic acid was lower among cases later developing IBD. Discussion: Smoking increases the risk of developing both UC and CD. Snuff use did not increase the risk for IBD, indicating that tobacco exposure is not the reason for increased IBD risk. Low ferritin indicates an early pathological process affecting iron storage unrelated to inflammation. Changes in vitamin B6 and tryptophan metabolites might indicate early pathological processes possibly related to gut microbiota changes. To conclude, this dissertation shows that multiple differences between individuals later developing IBD and controls can be seen years before IBD diagnosis. Some of which give insight to early pathophysiology in IBD.

In this paper, the algebraic topological characteristics of brain networks composed of electroencephalogram(EEG) signals induced by different quality images were studied, and on that basis, a neurophysiological image quality assessment approach was proposed. Our approach acquired quality perception-related neural information via integrating the EEG collection with conventional image assessment procedures, and the physiologically meaningful brain responses to different distortion-level images were obtained by topological data analysis. According to the validation experiment results, statistically significant discrepancies of the algebraic topological characteristics of EEG data evoked by a clear image compared to that of an unclear image are observed in several frequency bands, especially in the beta band. Furthermore, the phase transition difference of brain network caused by JPEG compression is more significant, indicating that humans are more sensitive to JPEG compression other than Gaussian blur. In general, the algebraic topological characteristics of EEG signals evoked by distorted images were investigated in this paper, which contributes to the study of neurophysiological assessment of image quality.

Periodontal disease is defined as a complex, multifactorial disease characterized by the loss of connective tissue attachment with destruction of periodontal tissues. The aim of periodontal therapy is to eliminate inflammatory process, prevent the progression of periodontal disease and also to regenerate the lost of periodontal tissues. Loss of the bone support by creating a periodontal pocket is one of the most common cause of tooth extraction. Their treatment can be conservative and surgical. The purpose of this paper is to demonstrate the treatment of infrabony periodontal defects with bone and soft tissue regeneration. On periodontal examination and radiographic evaluation, the female 56-year-old patient presented with an infrabony defect extending up to apical third of the mesial side of the right maxillary second molar with a probing depth of 8 mm. After conservative periodontal treatment, oral surgical intervention was performed including open flap debridement and filling the defect with xenograft and plasma rich fibrin. The application of xenograft and Plasma rich fibrin resulted in bone regeneration of the defect and successful fixed prosthodontic solution. Guided bone and soft tissue regeneration using xenograft and fibrin-rich plasma gives successful radiological and clinical signs of bone augmentation and consolidation of defects caused by loss of tooth attachment. Keywords: periodontal pocket, xenograft, PRF.

Herbal medicinal products are known for their widespread use toward various viral infections and ease of disease symptoms. Therefore, the sudden appearance of the Severe Acute Respiratory Syndrome-related Coronavirus 2 (SARS-CoV-2) and COVID-19 disease was no exception. Bioactive compounds from natural plant origin could act on several disease levels: through essential immunological pathways, affecting COVID-19 biomarkers, or by halting or modulating SARS-CoV-2. In this paper, we review the recently published data regarding the use of plant bioactive compounds in the prevention/treatment of COVID-19. The mode of actions responsible for these effects is discussed, including the inhibition of attachment, penetration and release of the virus, actions affecting RNA, protein synthesis and viral proteases, as well as other mechanisms. The reviewed information suggests that plant bioactive compounds can be used alone or in combinations, but upcoming, extensive and global studies on several factors involved are needed to recognize indicative characteristics and various patterns of bioactive compounds use, related with an array of biomarkers connected to different elements of inflammatory and immune-related processes of COVID-19 disease.

Introduction - The temporomandibular joint (TMJ)is a single paired joint that connects the jawbone to the skull. It is a bilateral synovial articulation between the temporal bone of the skull and the lower jaw; it is from these bones that his name originates. Temporomandibular dysfunction (TMD) is a collective term that includes a number of clinical problems involving the masseter muscle, TMJ and associated structures. Most often, occlusion is considered the main risk factor for the occurrence of TMD. There are studies on the association between dental malocclusion and the prevalence of TMD in orthodontic patients before and after orthodontic treatment. The most common types of dental malocclusions associated with TMD are deep bite, posterior crossbite, and anterior open bite. Aim - The aim of this paper is to analyze evidence from bibliography review on temporomandibular disorders in individuals with malocclusions. Materials and method - Systematic textbooks reviewn on temporomandibular joint dysfunction in malocclusions through available clinical trials, bibliography review, original research and articles published electronically in Pub Med and Google Scholar. Conclusion - According to data from the bibliography, it can be concluded that orthodontic treatment cannot be considered as a contributing factor to the development of temporomandibular disorders. Keywords: Temporomandibular joint, Temporomandibular disorders, Malocclusions

Benign prostatic hyperplasia is defined as a disorder, which has different ways of treatment depending on the symptomatology, the response to drug therapy, and the occurrence of complications. Pharmacological treatment of benign prostatic hyperplasia involves the use of mainly two groups of drugs: alpha 1 blockers and 5 alpha-reductase inhibitors (5ARIs). Side effects commonly occur during treatment with 5ARIs such as erectile dysfunction, decreased libido, and deterioration of psychological well-being. This paper aims to determine the association between DHEAS deficiency and the occurrence of side effects of 5ARI therapy that relate to the psychological well-being of patients with BPH. The analysis included 250 patients with benign prostatic hyperplasia (BPH), of whom 130 were treated with an alpha 1 blocker, while 120 patients were treated with a combination of tamsulosin and 5ARIs. The evaluation was conducted through questionnaires: IPSS (International Prostate Scoring System) to quantify BPH symptoms and PhQ-9 questionnaire for self-evaluation of depressive symptoms. The results showed that impaired psychological well-being occurred in 26 patients (22.5%) in the study group after 6- and 12-month therapy, which was statistically significant in this group (p

Benign prostatic hyperplasia (BPH) is the fourth most common disease in the male population aged over 50 years which results in lower urinary tract symptoms (LUTS). These symptoms lead to affect patients' quality of life (QoL) differently. Quality of life (QoL) refers to the subjective perception of a patient`s well-being in terms of physical, psychological, and socioeconomic aspects. Aging and worsening LUTS/BPH are contributing factors to decreased QoL. Several medicament options that include alpha-blockers and 5 alpha-reductase inhibitors as a "gold" standard, are available for LUTS/BPH treatment. This paper aims to evaluate the effects of pharmacological treatments used to treat LUTS /BPH in daily practice and to allow a comparison of results between treatments. We evaluated 250 patients with BPH using the International Prostate Symptom Score (IPSS) questionnaire, including the eighth question on quality of life concerning the severity of symptoms and the type of drug therapy with which they were treated. When analyzing the results, we concluded that patients with less pronounced symptoms of the disease have a better quality of life (p

Background and Objectives: The aim of the study was to explore the experiences of family carers of people with dementia (PWD) in Cyprus and to describe the impact of dementia on family carers using the International Classification of Functioning, Disability and Health (ICF) framework as a model to interpret the findings. Research Design and Methods: A questionnaire with multiple choice responses was developed based on previous work published by the Netherlands Institute for Health Services Research (NIVEL). Eighty-four family carers of PWD completed the questionnaire and sixteen others completed the pencil-paper version. The data were analyzed based on descriptive statistics. Results: The findings showed that family carers support PWD in several different life domains. The results from the questionnaire were mapped onto the ICF framework to determine the impact of dementia on carers’ lives. The results, according to the ICF, revealed that, on the whole, dementia carers experience negative changes to body function, activities and participation as a result of caring for PWD. Furthermore, family carers attribute the detrimental effects on their health and wellbeing to the impact of continuous care resulting from the dementia. Discussion and Implications: The findings provide valuable insight into the experiences of family carers of PWD in Cyprus, and the need for health professionals to support family carers. Taking into consideration the results of this study, dementia carers experience changes to their daily functioning because of the cared one’s health condition. This has been described as carer’s “third- party disability” in the literature.

Background Modern protocols for light sedation in combination with the increased number of COVID-19 infected patients hospitalized in Intensive Care Units (ICUs) have increased the number of patients who are mechanically ventilated and awake. Nurses require specific skills to care for this vulnerable group of patients. At the same time, nurses report feeling inadequate and frustrated when they attempt to establish communication with mechanically ventilated, conscious patients. Study objectives The purpose of this study was to explore the strategies nurses use when taking care of conscious, intubated patients in the intensive care unit and the barriers they encounter in their effort to communicate. Methods For this study, a qualitative design was employed. Data were collected using in-depth semi-structured interviews with 14 intensive care nurses working at ICUs in four different hospitals of Cyprus. The data were analyzed by applying thematic analysis. Results We identified several strategies of unaided (movements—lips, hands, legs—facial expressions, gestures, touching) and aided forms of communication (pen and paper, boards, tablets, mobiles) used by nurses to communicate with patients. However, barriers to communication were reported by the participating nurses mainly pertaining to patients and nurses’ characteristics as well as the ICU environment. The health protocols imposed by the pandemic added more obstacles to the communication between nurses and patients mostly related to the use of protective health equipment. Conclusions The results of this study point to the difficulties nurses in Cyprus face when trying to communicate with conscious patients during mechanical ventilation. It appears that the lack of nurses’ training and of appropriate equipment to facilitate augmentative and alternative communication leave the complex communication needs of critically ill patients unaddressed. However, further research including patients’ opinions, after they recover, would bring more clarity on this topic. Our study adds evidence to the communication crisis created by the protective health protocols imposed by the pandemic. As such, it highlights the need to educate nurses in augmentative and alternative ways of communication to address communication with mechanically ventilated, conscious patients during their ICU stay.

This paper describes a serious game based on a knowledge transfer model using deep reinforcement learning, with an aim to improve the caretakers’ knowledge and abilities in post-stroke care. The iTrain game was designed to improve caregiver knowledge and abilities by providing non-traditional training to formal and informal caregivers who deal with stroke survivors. The methodologies utilized professional medical experiences and real-life evidence data gathered during the duration of the iTrain project to create the scenarios for the game’s deep reinforcement caregiver behavior improvement model, as well as the design of game mechanics, game images and game characters, and gameplay implementation. Furthermore, the results of the game’s direct impact on caregivers (n = 25) and stroke survivors (n = 21) in Lithuania using the Geriatric Depression Scale (GDS) and user experience questionnaire (UEQ) are presented. Both surveys had favorable outcomes, showing the effectiveness of the approach. The GDS scale (score 10) revealed a low number of 28% of individuals depressed, and the UEQ received a very favorable grade of +0.8.

There is a growing tendency to place single tooth implants immediately after extracting a failing tooth in the posterior region. The aim of this article is to present the treatment and the one-year clinical follow-up of a patient. This case presentation illustrates a solution of rehabilitation option after maxillary bicuspid loss, including the diagnosis, treatment planning and the procedure of implantation. After the atraumatic extraction of the both maxillary premolars, we did a procedure for alveolar ridge preservation using a mixture of cortico-cancellous allograft and xenograft, and resorbable membrane (Maxgraft® and Mucoderm® by Botiss biomateratials GmbH, Germany) to enlarge the ridge and correct facial and socket defects, as well as thickening the peri-implant tissue. We used endosseous titanium self-tapping dental implants with conical shape, immediately placed after the act of extraction. The platform-switching helps preventing crestal bone loss, increases the volume of soft tissue around the implant platform and improves the esthetic end result. Bone and soft tissue defects were healed over time by wearing a long-term temporary crowns, titanium custom made abutments and final BruxZir® solid zirconia crowns. Conclusion: The paper highlights this combined approach in the placement of implants in fresh extraction sockets with good and stable esthetic and functional results. Keywords: Immediate implant placement, posterior region, extraction sites, ridge preservation

The clinical use of platelet-rich plasma (PRP) is based on increasing the concentration of growth factors and the secretion of proteins that can maximize the healing process at the cellular level. PRP is an autologous biological material, that involves minimal risk of immune reactions and transmission of infectious and contagious diseases, and it is widely used to repair musculoskeletal lesions and skin. Despite the great potential for applicability, the implementation of therapeutic inclusion of PRP as a clinical alternative has become difficult due to the lack of studies related to the standardization of production techniques, application conditions, and/or insufficient description of the adopted procedures. Currently, platelet-rich plasma therapy (PRP) is widely used and continues to grow for a variety of clinical applications. Along with its development, there are various options in the way of obtaining PRP, automatic or manual, while one of the most reliable methods according to the literature is the method of double centrifugation. Therefore, it is necessary to establish standard criteria to be met to obtain high-quality PRP, as well as several studies to determine the appropriate platelet concentration for different clinical applications. In this context, this paper aims to discuss some methodological aspects used to obtain PRP, as well as to discuss the bioactive properties of PRP and to point out its therapeutic use in various fields of regenerative medicine. Additionally, current techniques, critical points, technology for PRP preparation, and a review of the present deficiencies of this therapy that will need to be overcome if widely accepted, are described.

Pregnancy is a unique state of the female organism in which occur physiological changes that are necessary to maintain the pregnancy. To be able to respond to the increased metabolic needs of pregnancy and to maintain an adequate level of thyroid hormones in the blood, the thyroid gland responds with changes in its function and anatomy as well. Changes in thyroid function are mainly associated with increased levels of thyroxine-binding globulins in the blood. Their level increases as a result of estrogen stimulation in pregnancy and they are synthesized in the liver. Changes in the physiology of the thyroid gland during pregnancy also occur as a result of stimulation of the TSH receptors of the gland by the human chorionic gonadotropin hormone (hCG) which is secreted by the placental trophoblast. Due to the difference in the physiology of the thyroid gland in and outside of pregnancy, a special interpretation of the results of functional thyroid tests is required. Changes in hormone values are transitory, especially expressed in the first trimester of pregnancy. A healthy pregnant patient without thyroid pathology or disease compensates for those changes and a sufficient amount of thyroid hormones is produced. The presence of thyroid hormones in an optimal concentration in the blood maintains a successful pregnancy and secures normal neurological development of the fetus. Diseases of the thyroid gland lead to a decrease its compensatory ability during pregnancy and the contributes to the inability to respond to the increased metabolic needs that follow. The motive for this paper are the pregnant patients with undiagnosed or unrecognized thyroid gland diseases before pregnancy, where we encounter conditions when the thyroid gland cannot respond to the physiological changes that occur. One of the negative outcomes of this condition can be spontaneous pregnancy loss in the first trimester. Therefore, a special interpretation of the thyroid status in pregnancy is needed and the introduction of constant reference values that will apply only to pregnancy. World recommendations designate reference values for TSH and thyroid hormones respectively for each trimester of pregnancy, the so-called trimester-specific reference values. In case of absence of trimester-specific reference values, there are recommendations regarding the special interpretation of thyroid function tests and reference values; as well as recommendations for using adjusted values according to demographic characteristics that will apply to all trimesters. This review of literature recommendations would help in the management of patients in order to achieve an optimal serum level of thyroid-stimulating hormone and achieve a successful pregnancy, thus imposing the need to introduce recommendations in our laboratories for thyroid analysis values specific to pregnancy, which will differ from those for the non-pregnant population. Keywords: thyroid gland, thyrostimulating hormone, trimester-specific reference values

Objectives To outline the planning, development and optimisation of a psycho-educational behavioural intervention for patients on active surveillance for prostate cancer. The intervention aimed to support men manage active surveillance-related psychological distress. Methods The person-based approach (PBA) was used as the overarching guiding methodological framework for intervention development. Evidence-based methods were incorporated to improve robustness. The process commenced with data gathering activities comprising the following four components: • A systematic review and meta-analysis of depression and anxiety in prostate cancer • A cross-sectional survey on depression and anxiety in active surveillance • A review of existing interventions in the field • A qualitative study with the target audience The purpose of this paper is to bring these components together and describe how they facilitated the establishment of key guiding principles and a logic model, which underpinned the first draft of the intervention. Results The prototype intervention, named PROACTIVE, consists of six Internet-based sessions run concurrently with three group support sessions. The sessions cover the following topics: lifestyle (diet and exercise), relaxation and resilience techniques, talking to friends and family, thoughts and feelings, daily life (money and work) and information about prostate cancer and active surveillance. The resulting intervention has been trialled in a feasibility study, the results of which are published elsewhere. Conclusions The planning and development process is key to successful delivery of an appropriate, accessible and acceptable intervention. The PBA strengthened the intervention by drawing on target-user experiences to maximise acceptability and user engagement. This meticulous description in a clinical setting using this rigorous but flexible method is a useful demonstration for others developing similar interventions. Trial registration and Ethical Approval ISRCTN registered: ISRCTN38893965. NRES Committee South Central – Oxford A. REC reference: 11/SC/0355

Purpose The aim of the study was to present the systematic review and meta-analysis of the psychometrical analysis of Facial Disability Index (FDI) studies. Methods A literature search was conducted in the relevant electronic databases “PubMed, Scopus, Web of Science (WoS), and Cochrane Library.” A total of 621 articles were obtained by searching the relevant keywords (PubMed: 384, Cochrane Library: 14, Web of Science: 132, Scopus: 91). A total of 8 papers were included. The four-point classifcation and ratingbased “COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN)” tools were used to evaluate the bias risk and evidence levels. Results Cronbach’s alpha pooling of FDI total score was (ES): 0.803 (95% CI: 0.73–0.86). Heterogeneity for the Facial Disability Index-Physical Function (FDI-PF) and Facial Disability Index-Social Function (FDI-SF) subscore based on intraclass correlation coefcient (ICC) were I 2=84.2% (ICC: 0.88, 95% CI: 0.81–0.92) and I 2=73.7% (ICC: 0.87, 95% CI: 0.81–0.90), respectively. Correlational results between Sunnybrook Facial Grading System (SFGS) with FDI-PF and FDI-SF were 0.38 and 0.22, respectively. The correlations of FDI-PF with Short Form-12 Physical Component Summary (SF-12-PCS) and Short Form-12 Mental Health Component Summary (SF-12-MCS) were 0.43 and 0.28, respectively. Correlation results of FDI-SF with SF-12-PCS and SF-12-MCS were 0.23 and 0.57. The relationship results of Facial Clinimetric Evaluation with FDI-PF and FDI-SF were 0.71 and 0.57, respectively. Conclusion FDI is a psychometrically valuable questionnaire, especially for the internal consistency, reliability, and validity. In clinical practice, the use of FDI would be valuable, in addition to clinician-based grading, to see more of patients’ social infuences precisely.

The term developmental language disorder (DLD) refers to the condition in which a child fails to achieve the speech and language milestones that are expected for his/her chronological age. The disorder is often linked to a series of add-on effects such as learning difficulties, trouble with socializing, problematic behaviour and low self-esteem. According to the international literature, DLD affects approximately 7% of school children in mainstream education. This paper reports on research conducted in Cyprus aiming to map the services provided by speech and language therapists (SLTs) to children with DLD. A questionnaire containing key areas of enquiry was developed and distributed to professionals working with DLD in Cyprus. A total of 44 responses were submitted by SLTs who provide services to individuals with DLD. The findings showed that the majority of children with DLD are diagnosed with a mixed receptive/expressive language disorder and are, on average, 7 years of age. The speech therapy interventions provided by professionals were twice a week and were most often on an individual basis. The maximum number of sessions was not pre-determined. Findings underscored the need for further research in defining service provision issues for children with DLD in Cyprus. Refereed/Peer-reviewed

A presença de depressão aumenta o risco de fumar e vice-versa, sendo que metade dos fumadores que procura tratamento tem histórico de depressão. Os estados depressivos podem ser provocados ou exacerbados pela cessação do tabagismo e há evidência consistente nesse sentido. Deve ter-se em consideração que os fumadores não são um grupo homogéneo, por isso é importante desenvolver diferentes intervenções de cessação do tabagismo para grupos específicos, como pessoas com depressão major passada ou atual. O objetivo desta revisão foi resumir os achados de estudos publicados para chegar a uma conclusão acerca de quais intervenções de cessação do tabagismo são mais eficazes na redução dos sintomas depressivos nesta população específica e se os fumadores que se abstêm com sucesso correm risco de aumento da sintomatologia depressiva. Foi realizada uma revisão sistemática com base nas diretrizes do PRISMA. A pesquisa bibliográfica foi feita por meio de consultas às bases de dados Cochrane e PubMed, das quais foram incluídos oito artigos. A maioria encontrou melhoria da sintomatologia depressiva no subgrupo de fumadores que conseguiu parar de fumar. Além disso, o tratamento com ISRS foi associado à redução dos sintomas depressivos, em particular a sertralina atingiu significância estatística na redução da sintomatologia depressiva quando comparada com o placebo. Embora não seja possível tirar conclusões definitivas, esta revisão destaca algumas evidências de que a intervenção de cessação tabágica pode ser uma oportunidade realista para melhorar a sintomatologia depressiva e que a intervenção ativa com ISRS pode ser uma grande ajuda no tratamento. The presence of depression increases the risk for smoking and vice versa, according that half of smokers seeking treatment have a history of depression. Depressive states can be provoked or exacerbated by smoking cessation and there is consistent evidence in that direction. It must be taken into account that smokers are not a homogeneous group so that it is important to develop different smoking cessation interventions for specific groups, such as people with past or current major depression. The aim of this review was to summarize the findings from published studies to reach a conclusion of which smoking cessation interventions are more efective in reducing depressive symptoms in this specific population and if smokers who successfully abstain are at risk of increased depressive symptomatology. A systematic review was conducted based on PRISMA´s guidelines. A bibliographic search was made by quering Cochrane and PubMed databases from which were included eight papers. The majority found improvement of depressive symptomatology in the subgroup of smokers who attained to stop smoking. Moreover, SSRI treatment was associated with a reduction of depressive symptoms, in particular sertraline that reached statistical significance in reducing depressive symptomatology when compared with placebo. Even though it is not possible to draw definitive conclusions, this review highlights some evidence that smoking cessation intervention may be a realistic opportunity to improve depressive symptomatology and that active intervention with SSRI may be a big aid in treatment.

Background: A dor vesical crónica/Cistite Intersticial (DVC/CI) é uma doença crónica, comummente subdiagnosticada, com um importante impacto na qualidade de vida dos doentes. Mais recentemente, tem sido sugerida uma possível associação entre o VEGF e seus recetores na fisiopatologia de DVC/CI, devido ao papel que tem na promoção da angiogénese e inflamação, o que pode agravar a dor vesical. Eventualmente, o VEGF poderá ser usado como biomarcador para o diagnóstico e prognóstico da DVC/CI. Para clarificar esta questão, esta revisão tem como objetivo um resumo crítico da informação disponível, dando origem a um ponto de partida sólido para estudos futuros. Métodos: Nós pesquisamos sistematicamente Pubmed e Embase, usando as queries "urinary VEGF", "urinary VEGF" AND "pain", "urinary VEGF" AND "lower urinary tract symptoms" e "urinary VEGF" AND "LUTS", desde Janeiro de 2016 a Fevereiro de 2022. Resultados: Um total de 1026 artigos foram identificados, dos quais 7 artigos foram incluídos neste estudo que envolveu 1036 participantes. Relativamente aos níveis de VEGF, participantes com bexiga hiperativa (BHA) e participantes saudáveis foram usados para comparação com doentes DVC/CI. A concentração do VEGF urinário parece ser superior quando comparada com participantes saudáveis ou participantes com Bexiga Hiperativa (BHA). Níveis superiores de VEGF foram associados com a gravidade da dor, enquanto uma diminuição da concentração do VEGF está associada a uma melhoria da dor e dos sintomas em mulheres. No entanto, estes achados não foram constantes em todos os estudos. Conclusões: Há uma tendência para uma associação significativa entre níveis aumentados do VEGF e dor ou gravidade de sintomatologia em doentes DVC/CI. Embora haja algumas discrepâncias entre os estudos e o número de pacientes incluídos seja pequeno, o VEGF urinário e seus recetores deverão ser considerados para futuros estudos relativos ao seu uso na fisiopatologia, diagnóstico e prognóstico de DVC/CI. Background: Bladder pain syndrome/Interstitial cystitis (BPS/IC) is a chronic pain condition, often underdiagnosed, with an important impact on patient quality of life. More recently, it has been suggested an association between VEGF and its receptors in BPS/IC pathophysiology, due to their role in promoting angiogenesis and inflammation, which can enhance bladder pain. Eventually, VEGF may be used as a biomarker for the diagnosis and prognostication of BPS/IC. To further clarify this issue this review aims at critically summarizing the available information, giving rise to a solid starting point for future studies. Methods: We systematically searched PubMed and Scopus, using the queries "urinary VEGF", "urinary VEGF" AND "pain", "urinary VEGF" AND "lower urinary tract symptoms" and "urinary VEGF" AND "LUTS" from January 2016 to February 2022. Results: A total of 1026 papers were identified from which 7 articles were included in this study which assessed 1036 participants. Regarding VEGF levels, overactive bladder (OAB) and healthy patients were used for comparison with BPS/IC patients. VEGF concentration seems to be higher when compared to healthy patients and overactive bladder (OAB) patients. Higher levels of VEGF were associated with pain severity, while a decrease in VEGF concentration is associated with pain and symptom improvement in women. However, these findings were not constant in all studies. Conclusions: There is a trend towards a relevant association between increased VEGF levels and pain or symptom severity in BPS/IC patients. Although there are some discrepancies among the studies and the number of patients included is a small, VEGF and its receptors should be considered for future studies regarding its use in BPS/IC pathophysiology, diagnosis and prognostication.

With the introduction of computed tomography (CBCT) into daily dental practice, along with the development of software solutions in dentistry, it revolutionized the planning and protocol of dental implant placement. The development of the surgical guides and their use in the implantation procedure eliminated the possible complications that each implantologist may encounter during his work, such as injury to adjacent teeth, injury to vital anatomical structures, incorrect angulation and incorrect implant position of placed implants. This “guided implant therapy” ensures correct and proper positioning of the implants, shortens the time required for operative intervention, reduces post-operative morbidity, and eliminates the need for flap and bone grafting procedures. This paper will explain the complete procedure of planning and creating of surgical guide, present all the pros and cons of working with the guide and present a few clinical cases from daily practice.

Objetivos: Avaliar, através de uma revisão sistemática, os resultados a curto e longo prazo após reparação da válvula aórtica (RVA). Métodos: Realizámos uma revisão da literatura utilizando duas bases de dados. Foram incluídos estudos com tamanho amostral superior a 200, follow-up acima de 5 anos e com resultados de mortalidade e/ou reoperação. Séries pediátricas, de endocardite ou coarctação da aorta foram excluídas. Resultados: Dos 1729 artigos identificados, 22 foram incluídos. Dois estudos avaliaram RVA em válvulas bicúspides e um em disseção da aorta. Os restantes referiam-se a procedimentos da raiz da aorta (n=10) ou a amostras heterogéneas (n=9). O tamanho amostral variou entre 220 e 1015, totalizando 9965 pacientes. Relativamente aos resultados a curto-prazo, 2,3% dos pacientes morreram (reportado por 18 estudos), hemorragias ocorreram em 5,6% (14 estudos), isquemia miocárdica em 0,8% (9 estudos) e eventos neurológicos em 2,2% (17 estudos). Foi necessário pacemaker em 2,2% (9 estudos) e 16,2% dos pacientes desenvolveram insuficiência aórtica (11 estudos). As taxas de sobrevivência a 5, 10, 15 e 20 anos variam entre 86% e 99% (reportado em 10 estudos), 62% e 94% (15 estudos), 43% e 96% (6 estudos) e 70 % e 82% (3 estudos), respetivamente. A sobrevida-livre-de-reoperação a 5, 10, 15 e 20 anos variou entre 87% e 100% (11 estudos), 62% e 97% (17 estudos), 52% e 95% (8 estudos) e 70% e 95% (2 estudos), respetivamente. Conclusão: RVA pode ser considerada um procedimento seguro, revelando resultados satisfatórios a curto e longo-prazo. Objectives: To describe, through a systematic review, early and long-term outcomes after aortic valve repair (AVR). Methods: A literature review was performed using 2 databases. Studies with sample size above 200 patients, mean/median follow-up above 5 years and that reported mortality and/or reoperation outcomes were included. Papers addressing outcomes of pediatrics disease, endocarditis or aorta coarctation were excluded. Results: Out of 1729 titles identified, 22 were included. Two studies evaluated AVR in exclusively bicuspid aortic valves and one assessed AVR results for aortic dissection. The remaining studies focused on root procedures (n=10) or reported AVR in heterogeneous samples of patients presenting with aortic insufficiency (n=9). Studies' sample size ranged between 220 and 1015, totaling 9965 patients. Regarding early results, hospital mortality occurred in 2.3% of patients (reported by 18 studies), bleeding problems in 5.6% (14 studies), myocardial ischemia in 0.8% (9 studies) and neurological events in 2.2% (17 studies). Pacemaker implantation was needed in 2.2% (9 studies) and 16.2% of patients developed postoperative aortic insufficiency (11 studies). Survival rates at 5-, 10-, 15- and 20-years ranged between 86% and 99% (reported by 10 studies), 62% and 94% (15 studies), 43% and 96% (6 studies) and 70% and 82% (3 studies), respectively. Freedom from reoperation at 5-, 10-, 15-and 20- years rounded between 87% and 100% (11 studies), 62% and 97% (17 studies), 52% and 95% (8 studies) and 70% and 95% (2 studies), respectively. Conclusion: AVR can be considered a safe procedure, revealing satisfactory early and long-term outcomes.

RESUMO Introdução: A COVID-19 é uma doença pandémica com elevada mortalidade e morbilidade à escala global. É causada pelo vírus SARS-CoV-2, e as evidências mostram que este vírus afeta principalmente o trato respiratório, mas tem também impacto em outros órgãos do organismo humano. De facto, a maioria dos doentes COVID-19 apresentam vários outros sintomas além dos respiratórios, como neurológicos e cardiovasculares. As autópsias têm sido cruciais para delinear padrões de lesão associados à infecção, e o número de publicações que versa sobre a patologia aumenta diariamente. O objetivo desta revisão narrativa é sumariar os dados histopatológicos observados nos vários órgaos e sistemas através de uma revisão da literatura dos achados pós-morte de doentes COVID-19. Os achados de autópsia são uma ferramenta útil para a compreensão da doença, permitindo uma melhor gestão e tratamento dos doentes. Métodos: A revisão da literatura foi realizada de acordo as guidelines SANRA. Foram revistos os artigos com dados de autópsia e/ou biópsia realizadas em doentes com COVID-19, e a informação incluida foi organizada por órgãos e sistemas. Resultados: Os principais achados histopatológicos são dano alveolar difuso e microtrombos na vasculatura pulmonar. A análise histopatológica de outros órgãos também inclui presença de trombos e um grau variável de inflamação, como áreas focais de necrose de cardiomiócitos e ausência de padrão de miocardite evidente, esteatose hepática e lesão tubular aguda proximal a nível renal. Componentes víricos de SARS-CoV-2 como RNA e proteínas foram identificados em múltiplos órgãos. Conclusão: A COVID-19 afeta primordialmente o sistema respiratório, mas o vírus foi identificado em múltiplos órgãos e esta é uma doença reconhecidamente multiorgânica. Os resultados mostram que a maioria das alterações histopatológicas objetivadas nos diversos tecidos e órgãos não são específicos da COVID-19. Para além das alteraçoes a nível pulmonar, os efeitos extrapulmonares a curto e longo prazo do SARS-CoV-2 devem ser considerados e alvo de investigação mais aprofundada. Palavras-chave: Autópsia, COVID-19, SARS-COV-2. ABSTRACT Introduction: Coronavirus disease 2019 (COVID-19) is a global pandemic with substantial mortality and morbidity. It is caused by SARS-CoV-2 and evidence shows that the virus is not always confined to the respiratory tract and impacts the human body well beyond the lungs, showing an interplay with other organs. Indeed, the majority of COVID-19 patients show various other symptoms besides respiratory disorders including neurological and cardiovascular. Autopsies of patients who have died from COVID-19 have been crucial in delineating patterns of injury associated with SARS-CoV-2 infection and the number of publications regarding COVID-19 pathology is increasing daily. The aim of this narrative review is to address the currently available histopathological data and the postmortem findings of patients with COVID-19. The autoptic findings may represent useful tools to better understand the physiopathology of the disease as well as to improve patient management and treatment strategies. Methods: A literature review was conducted according to SANRA guidelines. Histopathological reports from deceased COVID-19 patients undergoing autopsy or biopsy were reviewed and papers that reported macroscopic and/or microscopic data in patients diagnosed with COVID-19 were considered. Data was sorted per organ system. Results: The major histological findings are tissue damage involving the lungs resulting in diffuse alveolar damage and intravascular microthrombi. Histopathologic examinations of other organs include microthrombi along with a variable degree of inflammation: dispersed area of cardiomyocyte necrosis with rare viral myocarditis pattern, hepatic steatosis and proximal acute tubule injury in renal tissues. Viral components (RNA, proteins) of SARS-CoV-2 were identified in multiple organs. Conclusion: COVID-19 affects not only the lungs and the virus can also be found in other organs and tissues. In terms of COVID-19 related pathological alterations the results demonstrate that the majority are not specific. In addition to pulmonary adverse reactions, short and long-term effects of SARS-CoV-2 on other organs should be considered and injuries of the extrapulmonary organs need further investigation. Keywords (Palavras-chave): Autopsy, COVID-19, SARS-CoV-2.

Background E-learning is recognised as a useful educational tool and is becoming more common in undergraduate medical education. This review aims to examine the scope and impact of e-learning interventions on medical student learning in clinical medicine, in order to aid medical educators when implementing e-learning strategies in programme curricula. Methods A systematic review compliant with PRISMA guidelines that appraises study design, setting and population, context and type of evaluations. Specific search terms were used to locate articles across nine databases: MEDLINE/PubMed, ScienceDirect, EMBASE, Cochrane Library, ERIC, Academic Search Complete, CINAHL, Scopus and Google Scholar. Only studies evaluating e-learning interventions in undergraduate clinical medical education between January 1990 and August 2021 were selected. Of the 4,829 papers identified by the search, 42 studies met the inclusion criteria. Results The 42 studies included varied in scope, cognitive domain, subject matter, design, quality and evaluation. The most popular approaches involved multimedia platforms (33%) and case-based approaches (26%), were interactive (83%), asynchronous (71%) and accessible from home (83%). Twelve studies (29%) evaluated usability, all of which reported positive feedback. Competence in use of technology, high motivation and an open attitude were key characteristics of successful students and preceptors. Conclusions Medical education is evolving consistently to accommodate rapid changes in therapies and procedures. In today’s technologically adept world, e-learning is an effective and convenient pedagogical approach for the teaching of undergraduate clinical medicine.

© 2022 Archives of Health Science and Research. All rights reserved.Objective: The visual system is one of the 3 most essential systems for maintaining balance. However, the evaluation of refractive error such as myopia has always been neglected in balance studies. This paper aimed to examine the differences in balance and proprioception measurements between individuals with myopia and their healthy peers. Materials and Methods: Fifteen subjects with myopic eye defects and 15 healthy peers were included in the study. Balance evaluations consisted of the tandem walk test (TWT), the limits of stability test (LOS), and the modified clinical test of sensory interaction and balance (mCTSIB). These evaluations were performed with a computer-aided NeuroCom Balance Master device. Additionally, proprioception was measured with the Biodex System 3 isokinetic dynamometer. Results: Individuals with myopic defects had higher step widths (P= .001), and end-sway (P = .007) than their healthy peers. The reaction time, maximum excursion, and directional control values of the myopia group were lower than those of the healthy peer group, but there was no difference between the results of the LOS and the m-CTSIB tests (P > .05 for all parameters). Moreover, the 60° proprioception evaluation deviation was higher in the myopia group for both dominant and non-dominant extremities. However, this deviation was not statistically significant (P > .05). Conclusion: This study showed some differences in the measured values for balance in myopic individuals compared to healthy peers. We think that the evaluation of the participants with the orthoses they use will provide more accurate results from the measurements in future studies evaluating balance and proprioception.

The attentional blink (AB) phenomenon reveals a bottleneck of human information processing: the second of two targets is often missed when they are presented in rapid succession among distractors. In our previous work, we showed that the size of the AB can be changed by applying transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (lDLPFC) (London & Slagter, Journal of Cognitive Neuroscience, 33, 756–68, 2021). Although AB size at the group level remained unchanged, the effects of anodal and cathodal tDCS were negatively correlated: if a given individual’s AB size decreased from baseline during anodal tDCS, their AB size would increase during cathodal tDCS, and vice versa. Here, we attempted to replicate this finding. We found no group effects of tDCS, as in the original study, but we no longer found a significant negative correlation. We present a series of statistical measures of replication success, all of which confirm that both studies are not in agreement. First, the correlation here is significantly smaller than a conservative estimate of the original correlation. Second, the difference between the correlations is greater than expected due to sampling error, and our data are more consistent with a zero-effect than with the original estimate. Finally, the overall effect when combining both studies is small and not significant. Our findings thus indicate that the effects of lDPLFC-tDCS on the AB are less substantial than observed in our initial study. Although this should be quite a common scenario, null findings can be difficult to interpret and are still under-represented in the brain stimulation and cognitive neuroscience literatures. An important auxiliary goal of this paper is therefore to provide a tutorial for other researchers, to maximize the evidential value from null findings.

The world over, people drink in order to socialize, celebrate, and relax, despite the negative health effects of alcohol. Three periods of dynamic brain changes are evidenced to be particularly sensitive to the harmful effects of alcohol: gestation (from conception to birth), later adolescence (15-19 years), and older adulthood (over 65 years). This article is concentrated only on the negative effects of alcohol in children who have been exposed to alcohol before birth, known as foetal alcohol syndrome (FAS). This is a review based on published data in PubMed over the last two decades and is an analysis of more than 150 published papers. Alcohol use during pregnancy can cause miscarriage, stillbirth, and a range of lifelong physical, be�havioural, and intellectual disabilities. The effects of ethanol are expressed on a set of molecules involved in neuroinflammation, myelination, neurotransmission, and neuron function. Modern neuroimaging techniques are able to specify some fine structural changes in the affected areas of the brain: volume reductions in the frontal lobe, including the middle frontal gyri in the prefrontal cortex, hippocampal structure, interhemispheric connectivity, abnormalities in glial cells, white matter deficits etc. Corpus callosum myelination is affected, resulting in a lack of the inter-hemispheric connectivity. This is known to facilitate autism, stroke, schizophrenia, as well as dementia, disrupts cognitive performance, and may lead to neurobehavioral deficits. It was pointed out that many symptoms and neuroimaging characteristics are similar in ADHD and FAS, thus the anamnesis for prenatal alcohol and nicotine exposure must be taken very seriously in order to better understand and interpret clinical symptoms.

Anatomical factors that narrow the upper airway predisposes for obstructive sleep apnea (OSA). Orthognathic surgery causes changes in the pharyngeal airway anda successful long-term treatment requires an understanding of all variables. This paper aims to describe the pharyngeal anatomy, factors that affects its dimension andconfiguration, discuss imaging of the pharynx with focus on computed tomography as well as normative volumetric data for healthy adults by 3-dimensional (3D)analysis. The literature search was performed in PubMed with following MeSH terms: "pharynx", “diagnostic imaging", “tomography, x-ray computed”, "imaging, threedimensional"and "adult” together with “upper airway” and “pharyngeal airway”. Articles evaluating the upper airway in relation to a surgical procedure or to specificdisease were excluded. A total of 46 articles were included and analyzed. As a fibromuscular tube, the size and shape of the pharynx is related to its mechanical intrinsic properties, surrounding anatomical structures and dynamic patientdependent factors, including breathing, gravity and postural changes, as well as technical aspects regarding imaging acquisition, processing and analysis by software.Even though 3D imaging allows cross-sectional and volumetric measurements, the current literature cannot present a consistent normative dimensional referencefor the pharyngeal airway. Airway size should be considered when planning orthognathic surgery in order to minimize negative side-effects. 3D imaging might provide a range of informationconcerning pharyngeal size and shapes that can be used to analyze what type and extension of surgical movement is necessary to optimize the treatment. A standardprotocol for 3D assessment of the pharyngeal airway is still missing and clinical research with good quality and standardized criteria are needed.

Background: The brain is susceptible to hypoxic-ischemic brain injury in conjuction with out-of-hospital cardiac arrest (OHCA). Cognitive impairments are documented in about half of all OHCA survivors, however with a pronounced heterogeneity in measurements and findings. More detailed studies and instruments that are sensitive to OHCA-related cognitive impairment, including predictive models to identify individuals at risk, are needed. It is also unclear how different neurocognitive outcome methods are related to each other, to the brain injury, and to associated factors.Aims: The overall aim of this thesis was to explore the extent of neurocognitive impairment following OHCA in the late recovery phase. Specific aims per papers included in this thesis were: I) To examine the psychometric properties of an observer-reported questionnaire modified for usage after cardiac arrest, the Informant Questionnaire on Cognitive Decline in the Elderly-Cardiac Arrest (IQCODE-CA). II) To explore associations between four neurocognitive outcome methods administered in the late recovery phase and early hypoxic-ischemic brain injury assessed by the biomarker serum neurofilament light (NFL), and to compare the agreement for the four outcome methods. III) To describe the rationale and, IV) report initial results of detailed assessment of neurocognitive impairment in OHCA survivors, compare the cognitive performance to a cohort of participants following acute myocardial infarction (MI), and investigate the relationship between cognitive performance and the associated factors of emotional problems, fatigue, insomnia, and cardiovascular risk factors.Methods: I & II) Post-hoc analyses of surviving participants of the international multicenter Target temperature management 33 °C versus 36 °C after out-of-hospital cardiac arrest trial (TTM-trial), its biobank, and its cognitive sub-study, with a follow-up at 6 months post-arrest. III & IV) Prospective inclusion of surviving participants of the international multicenter Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest trial (TTM2-trial) at neuropsychological sub-study sites, recruitment of a matched non-arrest control group with acute MI, and an extensive neuropsychological assessment at approximately 7 months post-cardiac event.Results: I) The IQCODE-CA had acceptable psychometric properties and may be used alongside with performance-based measures when screening for post-arrest cognitive impairment. II) The clinician-report Cerebral Performance Category was mostly related to brain injury according to NFL, but with a ceiling effect. Although associations between patient-reports and performance-based measures were weak, all four outcome methods correlated significantly with each other. III & IV) Cognitive impairment on neuropsychological tests was generally mild among OHCA survivors (29% had at least borderline–mild impairment in ≥ 2 cognitive domains, and 14% had major impairment in ≥ 1 cognitive domain), but most pronounced in episodic memory, executive functions, and processing speed. OHCA survivors performed worse than MI controls. Diabetes and symptoms of anxiety, depression, and fatigue were associated with worse cognitive performance among the OHCA survivors.Conclusions: Cognitive impairment following OHCA is common. A post-OHCA follow-up service should screen for cognitive impairment using different neurocognitive outcome methods with acceptable psychometric properties. Since cognitive impairment is interrelated with emotional problems and fatigue, these areas should also be covered within routine screening. Patients with signs of impairment could be referred to neuropsychological assessment or team-based cognitive rehabilitation programs to optimize their recovery and long-term outcome.

The first human cases of coronavirus disease (COVID-19), a disease caused by the new coronavirus, were first reported on December 31, 2019 in China. Тhe virus was named temporary as 2019 new coronavirus (2019 novel coronavirus-2019 -nCoV), or finally as SARS-CoV-2. The aim of this paper is to give an overview of the laboratory detection of SARS-CoV-2 virus with Reverse Transcriptase - Polymerase Chain Reaction (RT-PCR) in real time, as well as detection of viral mutations. The samples used in the study were taken from all geographical regions in RNM, including the 10 regional Centers for Public Health throughout the country, hospital patients from COVID19 hospitals across the country and from the COVID19 checkpoint at the Institute of Public Health. All samples were tested using RT-PCR in real time. Additional assays have been applied for the identification of the circulating variants. The continuous surveillance of the variants of concern (VOC),as well as the newly emerged variants can allow for the public health officials to modify their approach to disease control and management and intervene more effectively as well as in a timely manner in order to prevent major morbidity and mortality from COVID-19.

High Flow Nasal Oxygen (HFNO) therapy offers a proven means of delivering respiratory support to critically ill patients suffering from viral illness such as COVID-19. However, the therapy has the potential to modify aerosol generation and dispersion patterns during exhalation and thereby put healthcare workers at increased risk of disease transmission. Fundamentally, a gap exists in the literature with regards to the effect of the therapy on the fluid dynamics of the exhalation jet which is essential in understanding the dispersion of aerosols and hence quantifying the disease transmission risk posed by the therapy. In this paper, a multi-faceted approach was taken to studying the aerosol-laden exhalation jet. Schlieren imaging was used to visualise the flow field for a range of expiratory activities for three healthy human volunteers receiving HFNO therapy at flow rates of 0—60 L/min. A RANS turbulence model was implemented using the CFD software OpenFOAM and used to perform a parametric study on the influence of exhalation velocity and duration on the dispersion patterns of non-evaporating droplets in a room environment. A dramatic increase in the turbulence of the exhalation jet was observed when HFNO was applied. Quantitative analysis indicated that the mean exhalation velocity was increased by 2.2—3.9 and 2.3—3 times that for unassisted breathing and coughing, respectively. A 1—2 second increase was found in the exhalation duration. The CFD model showed that small droplets (10—40 μm) were most greatly affected, where a 1 m/s increase in velocity and 1 s increase in duration caused an 80% increase in axial travel distance.