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Background and Aims: Although the Netherlands, Canada and Australia were early adopters of harm reduction for people who inject drugs (PWID), their respective HIV and hepatitis C (HCV) epidemics differ. We measured the pooled effect of needle and syringe program (NSP) and opioid agonist therapy (OAT) participation on HIV and HCV incidence in these settings. Design: For each cohort, we emulated the design and statistical analysis of a target trial using observational data. Setting and Participants: We included PWID at risk of HIV or HCV infection from the Amsterdam Cohort Studies (1985–2013), Vancouver Injection Drug Users Study (1997–2009) and Melbourne Injecting Drug User Cohort Study (SuperMIX) (2010–2021). Measurements: Separately for each infection and cohort (only HCV in SuperMIX), marginal structural models were used to compare the effect of comprehensive (on OAT and 100% NSP coverage or on OAT only if no recent injection drug use) versus no/partial NSP/OAT (no OAT and/or

Objective: To disclose the nature of cognitive deficits in a cohort of patients with idiopathic autonomic failure (IAF) by exploring the relation among cognitive functions, cardiovascular autonomic failure (AF) and clinical progression to another α-synucleinopathy (phenoconversion). Methods: We retrospectively identified all patients with a clinical diagnosis of IAF who underwent a comprehensive neuropsychological evaluation, clinical examination and cardiovascular autonomic tests from the IAF-BO cohort. Brain magnetic resonance imaging (MRI) studies and cerebrospinal fluid (CSF) analysis, including neurofilament light chain (NfL), Alzheimer disease core biomarkers, and α-synuclein seeding activity were further evaluated when available. Correlations among cognitive functions, clinical features, cardiovascular AF, cerebral white matter hyperintensities (WMH) load, and CSF biomarkers were estimated using Spearman correlation coefficient. Results: Thirteen out of 30 (43%) patients with IAF displayed cognitive deficits (CI) mainly concerning executive functioning. Seven out of 30 (23%) met the criteria for mild cognitive impairment (MCI). The diagnosis of CI and MCI was not associated with phenoconversion or autonomic function parameters, including duration and severity of neurogenic orthostatic hypotension, presence and severity of supine hypertension, and nocturnal dipper profile. Twenty patients underwent a brain MRI and CSF analysis. MCI was related to WMH load (r = 0.549) and NfL levels (r = 0.656), while autonomic function parameters were not associated with either WMH or NfL levels. Interpretation: Cardiovascular AF and phenoconversion, underlying the spreading of neurodegeneration to the central nervous system, were not independent drivers of cognitive dysfunction in IAF. We identified WMH load and NfL levels as potential biomarkers of the neural network disruption associated with cognitive impairment in patients with IAF.

O principal objetivo do tratamento endodôntico é alcançar um ambiente livre de bactérias por meio das soluções irrigantes, preparo biomecânico e medicações intracanais. O hidróxido de cálcio é amplamente utilizado como medicação intracanal por apresentar propriedades antimicrobianas e biológicas adequadas ao tratamento endodôntico, normalmente associado a um veículo que permita sua inserção nos canais radiculares. Assim, o objetivo deste estudo foi avaliar a atividade antimicrobiana do hidróxido de cálcio associada a diferentes veículos sobre biofilme de Enterococus faecalis. Foram confeccionados 90 espécimes de dentina, que permaneceram em placas contendo meio de cultura inoculado com Enterococus faecalis para permitir a formação de biofilme. Decorridos 21 dias, os espécimes foram lavados em solução salina e transferidos para uma nova placa onde as medicações com os diferentes veículos a serem testados foram colocados sobre o biofilme. As placas de cultura foram deixadas em estufa a 37°C por 7, 14 e 21 dias. Espécimes sem aplicação de medicação foram utilizados como controle para cada tempo experimental. Após cada tempo experimental de contato com os veículos, os espécimes foram lavados em solução salina, agitados em vortex, diluídos e plaqueadas em triplicata em meio de cultura específicos. As unidades formadoras de colônias foram contadas e analisadas estatisticamente (p

Introduction: Lewy body disease (LBD) is the second most common neurodegenerative disorder in patients older than 65 years. LBD is characterized by heterogeneous symptoms like fluctuation in attention, visual hallucinations, Parkinsonism, and REM sleep behaviour disorders. Considering the relevant social impact of the disease, identifying effective non-pharmacological treatments is becoming a priority. The aim of this systematic review was to provide an up-to-date literature review of the most effective non-pharmacological treatments in patients with LBD, focussing on evidence-based interventions. Methods: Following PRISMA criteria, we carried out a systematic search through three databases (PubMed, Cochrane Libraries, and PEDro) including physical therapy (PT), cognitive rehabilitation (CR), light therapy (LT), transcranial direct current stimulation (tDCS), transcranial magnetic stimulation (TMS), electroconvulsive therapy (ECT), deep brain stimulation (DBS). All studies were qualitatively assessed using standardized tools (CARE and EPHPP). Results: We obtained a total of 1,220 studies of which 23 original articles met eligibility criteria for inclusion. The total number of LBD patients included was 231; mean age was 69.98, predominantly men (68%). Some PT studies highlighted improvements in motor deficits. CR produced significant improvements in mood, cognition, and patient’s quality of life and satisfaction. LT outlined a partial trend of improvements in mood and sleep quality. DBS, ECT, and TMS showed some partial improvements mainly on neuropsychiatric symptoms, whereas tDCS provided partial improvements in attention. Conclusion: This review highlights the efficacy of some evidence-based rehabilitation studies in LBD; however, further randomized controlled trials with larger samples are needed to provide definitive recommendations.

A presente proposta objetivou usar os equipamentos didático-tecnológicos destinados ao auxílio do ensino da tecnologia Arduino para o Ensino Médio. Quanto à metodologia, a linguagem de programação Arduino, as ligações eletrônicas necessárias e a explicação do sistema Tinkercad foram trabalhadas de forma prática e dialogadas com o auxílio da plataforma de prototipagem eletrônica, relacionando o conteúdo e a tecnologia durante as aulas. Inicialmente, nos projetos, os encontros foram planejados para serem aplicados mensalmente a turmas provenientes do Ensino Médio público, visando aumentar o índice de conhecimento dessa plataforma. No entanto, a quarentena imposta pela pandemia da Covid-19 nos forçou a readequar o plano, assim, utilizaram-se gravações, postagens de vídeos e aulas remotas síncronas para dar prosseguimento ao trabalho. Os resultados alcançados foram diretamente ligados à melhoria do ensino, tornando-o mais dinâmico e atrativo, direcionando o olhar, o interesse, as inquietações e questionamentos dos alunos para este campo científico e tecnológico.

Binary Quadratic Program with Variable Partitioning Constraints The binary quadratic program with variable partitioning constraints is a very general class of optimization problems that is very difficult to solve because of the nonconvexity and integrality of the variables and is ubiquitous, among others, in network design, computer vision, and transportation and logistics. In their article, “A convex reformulation and an outer approximation for a large class of binary quadratic programs,” Rostami et al. show how to transform such a nonconvex challenging problem into a convex bilinear program with decomposable structure. The authors develop a branch-and-cut algorithm based on outer approximation cuts, in which the cuts are generated on the fly by efficiently solving separation subproblems. The results of their computational experiments on different problems confirm the efficacy of the solution methods in solving large-scale problem instances.

The aim of our study was to compare compressed sensing (CS) time-of-flight (TOF) magnetic resonance angiography (MRA) with parallel imaging (PI) TOF MRA in the evaluation of patients with intracranial aneurysms treated with coil embolization or stent-assisted coiling. We enrolled 22 patients who underwent follow-up imaging after intracranial aneurysm coil embolization. All patients underwent both PI TOF and CS TOF MRA during the same examination. Image evaluation aimed to compare the performance of CS to PI TOF MRA in determining the degree of aneurysm occlusion, as well as the depiction of parent vessel and vessels adjacent to the aneurysm dome. The reference standard for the evaluation of aneurysm occlusion was PI TOF MRA. The inter-modality agreement between CS and PI TOF MRA in the evaluation of aneurysm occlusion was almost perfect (κ  =  0.98, p  <  0.001) and the overall inter-rater agreement was substantial (κ  =  0.70, p  <  0.001). The visualization of aneurysm parent vessel in CS TOF images compared with PI TOF images was evaluated to be better in 11.4%, equal in 86.4%, and worse in 2.3%. CS TOF MRA, with almost 70% scan time reduction with respect to PI TOF MRA, yields comparable results for assessing the occlusion status of coiled intracranial aneurysms. Short scan times increase patient comfort, reduce the risk of motion artifacts, and increase patient throughput, with a resulting reduction in costs. CS TOF MRA may therefore be a potential replacement for PI TOF MRA as a first-line follow-up examination in patients with intracranial aneurysms treated with coil embolization.

Introduction: Marfan syndrome (MFS) is the most common inherited connective tissue disorder and its association with intracranial aneurysms (ICAs) has been debated for more than two decades. Here, we report the prevalence of ICAs at screening neuroimaging in a population of genetically confirmed MFS patients and present the results of a meta-analysis including our cohort of patients and those of previous studies. Patients and methods: We enrolled 100 consecutive MFS patients, who underwent screening with brain magnetic resonance angiography at our tertiary center between August 2018 and May 2022. We did a PubMed and Web of Science search to retrieve all studies on the prevalence of ICAs in patients with MFS published before November, 2022. Results: Of the 100 patients included in this study (94% Caucasians, 40% females, mean age 38.6 ± 14.6 years), three had an ICA. We pooled the current study with five previously published studies, including a total of 465 patients, 43 of which harbored at least one unruptured ICA, leading to an overall ICA prevalence of 8.9% (95% CI 5.8%–13.3%). Discussion and conclusion: In our cohort of genetically confirmed MFS patients, the prevalence of ICAs was 3%, which is substantially lower compared to previous studies based on neuroimaging. The high frequency of ICA found in previous studies could be explained by selection bias and lack of genetic testing, which may have led to the inclusion of patients with different connective tissue disorders. Further studies, including several centers and a large number of patients with genetically confirmed MFS, are needed to confirm our results.

Tujuan penelitian adalah untuk mengetahui budaya organisasi dan lingkungan kerja berpengaruh terhadap kepemimpinan pada Dinas Sosial Provinsi Sulawesi Selatan, untuk mengetahui budaya organisasi, lingkungan kerja, dan kepemimpinan berpengaruh terhadap kinerja pegawai pada Dinas Sosial Provinsi Sulawesi Selatan, serta untuk mengetahui budaya organisasi dan lingkungan kerja berpengaruh terhadap kinerja pegawai dimediasi kepemimpinan pada Dinas Sosial Provinsi Sulawesi Selatan. Data yang digunakan adalah data primer dan data sekunder. Sampel dalam penelitian ini adalah pegawai negeri sipil pada Dinas Sosial Provinsi Sulawesi Selatan yang berjumlah 95 orang berdasarkan rumus Slovin. Pengumpulan data dilakukan melalui observasi, kuesioner, dan dokumentasi. Metode analisis data menggunakan teknik analisis Partial Least Square/Smart PLS dan pengujian hipotesis mediasi yakni Uji Sobel Test. Hasil penelitian menunjukkan bahwa budaya organisasi dan lingkungan kerja berpengaruh positif dan signifikan terhadap kepemimpinan pada Dinas Sosial Provinsi Sulawesi Selatan, bahwa budaya organisasi, lingkungan kerja, dan kepemimpinan berpengaruh positif dan signifikan terhadap kinerja pegawai pada Dinas Sosial Provinsi Sulawesi Selatan, serta bahwa budaya organisasi dan lingkungan kerja berpengaruh positif dan signifikan terhadap kinerja pegawai dimediasi kepemimpinan pada Dinas Sosial Provinsi Sulawesi Selatan. The purpose of the study was to find out how organizational culture and work environment affect leadership at the Social Service of South Sulawesi Province, to find out how organizational culture, work environment, and leadership affect employee performance at the Social Service of South Sulawesi Province, and to find out how organizational culture and work environment have an effect. on employee performance mediated by leadership at the Social Service of South Sulawesi Province. The data used are primary data and secondary data. The sample in this study were civil servants at the Social Service of South Sulawesi Province, totaling 95 people based on the Slovin formula. Data was collected through observation, questionnaires, and documentation. The data analysis method used the Partial Least Square/Smart PLS analysis technique and the mediation hypothesis testing, namely the Sobel Test. The results showed that organizational culture and work environment had a positive and significant effect on leadership at the Social Service of South Sulawesi Province, that organizational culture, work environment, and leadership had a positive and significant effect on employee performance at the Social Service of South Sulawesi Province, and that organizational culture and work environment has a positive and significant effect on employee performance mediated by leadership at the Social Service of South Sulawesi Province.

To date there has been limited head-to-head evaluation of immune responses to different types of COVID-19 vaccines. A real-world population-based longitudinal study was designed with the aim to define the magnitude and duration of immunity induced by each of four different COVID-19 vaccines available in Italy at the time of this study. Overall, 2497 individuals were enrolled at time of their first vaccination (T0). Vaccine-specific antibody responses induced over time by Comirnaty, Spikevax, Vaxzevria, Janssen Ad26.COV2.S and heterologous vaccination were compared up to six months after immunization. On a subset of Comirnaty vaccinees, serology data were correlated with the ability to neutralize a reference SARS-CoV-2 B strain, as well as Delta AY.4 and Omicron BA.1. The frequency of SARS-CoV-2-specific CD4+ T cells, CD8+ T cells, and memory B cells induced by the four different vaccines was assessed six months after the immunization. We found that mRNA vaccines are stronger inducer of anti-Spike IgG and B-memory cell responses. Humoral immune responses are lower in frail elderly subjects. Neutralization of the Delta AY.4 and Omicron BA.1 variants is severely impaired, especially in older individuals. Most vaccinees display a vaccine-specific T-cell memory six months after the vaccination. By describing the immunological response during the first phase of COVID-19 vaccination campaign in different cohorts and considering several aspects of the immunological response, this study allowed to collect key information that could facilitate the implementation of effective prevention and control measures against SARS-CoV-2.

BACKGROUND: Immediate initiation of antiretroviral therapy (ART) regardless of CD4 cell count reduces risk for AIDS and non-AIDS-related events in asymptomatic, HIV-positive persons and is the standard of care. However, most HIV-positive persons initiate ART when their CD4 count decreases below 500 × 10 9 cells/L. Consequences of delayed ART on risk for non-AIDS-defining and AIDS-defining cancer, one of the most common reasons for death in HIV, are unclear. OBJECTIVE: To estimate the long-term risk difference for cancer with the immediate ART strategy.DESIGN: Multinational prospective cohort study.SETTING: The D:A:D (Data collection on Adverse events of anti-HIV Drugs) study, which included HIV-positive persons from Europe, Australia, and the United States.PARTICIPANTS: 8318 HIV-positive persons with at least 1 measurement each of CD4 cell count and viral load while ART-naive (study period, 2006 to 2016).MEASUREMENTS: The parametric g-formula was used, with adjustment for baseline and time-dependent confounders (CD4 cell count and viral load), to assess the 10-year risk for non-AIDS-defining and AIDS-defining cancer of immediate versus deferred (at CD4 counts RESULTS: During 64 021 person-years of follow-up, 231 cases of non-AIDS-defining cancer and 272 of AIDS-defining cancer occurred among HIV-positive persons with a median age of 36 years (interquartile range, 29 to 43 years). With immediate ART, the 10-year risk for non-AIDS-defining cancer was 2.97% (95% CI, 2.37% to 3.50%) and that for AIDS-defining cancer was 2.50% (CI, 2.37% to 3.38%). Compared with immediate ART initiation, the 10-year absolute risk differences when deferring ART to CD4 counts less than 500 × 10 9 cells/L and less than 350 × 10 9 cells/L were 0.12 percentage point (CI, -0.01 to 0.26 percentage point) and 0.29 percentage point (CI, -0.03 to 0.73 percentage point), respectively, for non-AIDS-defining cancer and 0.32 percentage point (CI, 0.21 to 0.44 percentage point) and 1.00 percentage point (CI, 0.67 to 1.44 percentage points), respectively, for AIDS-defining cancer. LIMITATION: Potential residual confounding due to observational study design.CONCLUSION: In this young cohort, effects of immediate ART on 10-year risk for cancer were small, and further supportive data are needed for non-AIDS-defining cancer.PRIMARY FUNDING SOURCE: Highly Active Antiretroviral Therapy Oversight Committee.

Despite modern solvers being able to tackle mixed-integer quadratic programming problems (MIQPs) for several years, the theoretical and computational implications of the employed resolution techniques are not fully grasped yet. An interesting question concerns the choice of whether to linearize the quadratic part of a convex MIQP: although in theory no approach dominates the other, the decision is typically performed during the preprocessing phase and can thus substantially condition the downstream performance of the solver. In “A Classifier to Decide on the Linearization of Mixed-Integer Quadratic Problems in CPLEX,” Bonami, Lodi, and Zarpellon use machine learning (ML) to cast a prediction on this algorithmic choice. The whole experimental framework aims at integrating optimization knowledge in the learning pipeline and contributes a general methodology for using ML in MIP technology. The workflow is fine-tuned to enable online predictions in the IBM-CPLEX solver ecosystem, and, as a practical result, a classifier deciding on MIQP linearization is successfully deployed in CPLEX 12.10.0.

Somatic mutations are a major source of cancer development, and many driver mutations have been identified in protein coding regions. However, the function of mutations located in miRNA and their target binding sites throughout the human genome remains largely unknown. Here, we built detailed cancer-specific miRNA regulatory networks across 30 cancer types to systematically analyze the effect of mutations in miRNAs and their target sites in 3′ untranslated region (3′ UTR), coding sequence (CDS), and 5′ UTR regions. A total of 3,518,261 mutations from 9,819 samples were mapped to miRNA–gene interactions (mGI). Mutations in miRNAs showed a mutually exclusive pattern with mutations in their target genes in almost all cancer types. A linear regression method identified 148 candidate driver mutations that can significantly perturb miRNA regulatory networks. Driver mutations in 3′UTRs played their roles by altering RNA binding energy and the expression of target genes. Finally, mutated driver gene targets in 3′ UTRs were significantly downregulated in cancer and functioned as tumor suppressors during cancer progression, suggesting potential miRNA candidates with significant clinical implications. A user-friendly, open-access web portal (mGI-map) was developed to facilitate further use of this data resource. Together, these results will facilitate novel noncoding biomarker identification and therapeutic drug design targeting the miRNA regulatory networks. Significance: A detailed miRNA–gene interaction map reveals extensive miRNA-mediated gene regulatory networks with mutation-induced perturbations across multiple cancers, serving as a resource for noncoding biomarker discovery and drug development.

O tratamento cirúrgico da úlcera péptica é reservado para úlcera péptica refratária ao tratamento clínico e/ou endoscópico, para suspeita de malignidade dentro de uma úlcera ou para o tratamento de complicações da úlcera péptica. Os pacientes com úlcera duodenal e indicação de cirurgia eletiva, sugere-se a vagotomia em vez de outro procedimento de redução de ácido. A vagotomia reduz o risco de ulceração recorrente, minimizando as complicações pós-operatórias e as sequelas a longo prazo. Para pacientes com úlcera duodenal hemorrágica que receberam tratamento médico adequado, sugere-se realizar uma vagotomia troncular e piloroplastia após o controle do sangramento, em vez de outro procedimento. O manejo do leito da úlcera sozinho para controlar o sangramento é apropriado em pacientes hemodinamicamente instáveis, pacientes com comorbidades significativas que limitam a expectativa de vida e pacientes com infecção por Helicobacter pylori não tratada. A compreensão do manejo cirúrgico continua sendo importante, uma vez que a cirurgia é a base do tratamento de emergência dessas complicações com risco de vida e para doenças refratárias ao tratamento médico.

Introdução: Uma unidade de terapia intensiva requer cuidados especiais e atuação de enfermeiros qualificados. Objetivos: Conhecer as percepções do enfermeiro diante da morte dentro de uma Unidade de Terapia Intensiva Neonatal e suas estratégias de enfrentamento. Métodos: Trata-se de um estudo descritivo, qualitativo onde os sujeitos da pesquisa foram constituídos por sete enfermeiros que trabalhavam em uma Unidade de Terapia Intensiva Neonatal de um hospital de grande porte do município de Piracicaba-SP. Os dados foram produzidos em entrevista semiestruturada utilizando roteiro, registrados em gravação, transcritos na íntegra e analisados mediante a técnica de análise de conteúdo. Resultados: A análise interpretativa das entrevistas possibilitou a construção de três categorias: 1) dificuldades em lidar com a morte; 2) o significado de morte digna; e 3) estratégias de enfrentamento do enfermeiro para vivenciar a morte na Unidade de Terapia Intensiva Neonatal. Conclusão: Para a maioria das enfermeiras entrevistadas, a morte dentro da UTIN gera sentimento de impotência e angústia. Faz-se necessário que os profissionais atuantes na UTIN, sejam especialistas nesse ambiente de trabalho, e que as instituições de saúde ofereçam suporte psicológico para que seu funcionário saiba lidar junto a equipe e com a família da melhor forma possível essa triste realidade.

International audience; Introductory programming courses (CS1) are difficult for novices. Inspired by Problem solving followed by instruction and Productive Failure approaches, we define an original "necessity driven" learning design. Students are put in an apparently well-known situation, but this time they miss an essential ingredient (the target concept) to solve the problem. Then, struggling to solve it, they experience the necessity of that concept. A direct instruction phase follows. Finally, students return to the problem with the necessary knowledge to solve it. In a typical CS1 learning path, we recognise a challenging "rollercoaster of abstraction". We provide examples of learning sequences designed with our approach to support students when the abstraction changes (both upward and downward) inside the programming language, for example, when a new construct (and the related syntactical, conceptual, and strategic knowledge) is introduced. Also, we discuss the benefits of our design in light of Informatics education literature.

Lisa Taruffi,1,&ast; Lorenzo Muccioli,1,&ast; Micaela Mitolo,2,3 Lorenzo Ferri,1 Carlo Descovich,4 Stefania Mazzoni,2 Roberto Michelucci,2 Raffaele Lodi,1,2 Rocco Liguori,1,2 Pietro Cortelli,1,2 Caterina Tonon,1,2 Francesca Bisulli1,2 1Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; 2IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; 3Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy; 4Clinical Governance, Research, Education and Quality Improvement Unit, AUSL Bologna, Bologna, Italy&ast;These authors contributed equally to this workCorrespondence: Francesca Bisulli, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy, Tel +39 0514966937, Fax +39 05149669993, Email francesca.bisulli@unibo.itPurpose: We report our single-center experience on the neurological manifestations of long COVID.Patients and Methods: This is a retrospective observational study. All consecutive patients referred to the neurological long COVID outpatient clinic of our institute from January 21 2021 to December 9 2021 underwent a general neurological objective examination. Treatments and investigations (brain MRI, neuropsychological evaluation, or others) were prescribed on an individual basis as per standard clinical practice. A follow-up visit was performed when appropriate. Descriptive statistics were presented as absolute and relative frequencies for categorical variables and as means, median, and ranges for continuous variables.Results: One hundred and three patients were visited (mean age 50.5 ± 36 years, 62 females). The average time from acute COVID-19 infection to the first visit to our outpatient clinic was 243 days. Most patients presented with a mild form of acute COVID-19, with only 24 cases requiring hospitalization. The neurological symptoms mostly (n=70/103, 68%) started during the acute phase (before a negative swab for SARS-CoV-2). The most frequent acute manifestations reported, which lately became persistent, were fatigue (n=58/103, 56%), olfactory/taste dysfunction (n=58/103, 56%), headache (n=47/103, 46%), cognitive disorders (n=46/103, 45%), sleep disorders (n=30/103, 29%), sensitivity alterations (n=29/103, 28%), and dizziness (n=7/103, 7%). Tremor was also reported (n=8/103, 7%). Neuropsychological evaluation was performed in 30 patients and revealed alterations in executive functions (n=6/30, 20%), memory (n=11/30, 37%), with pathological depressive (n=9/30, 30%) and anxiety (n=8/30, 27%) scores. Brain MRIs have been performed in 41 cases, revealing nonspecific abnormal findings only in 4 cases. Thirty-six patients underwent a follow-up, where a general improvement was observed but rarely (n=2/36) a complete recovery.Conclusion: The majority of patients presenting persistent neurological symptoms (most frequently fatigue, cognitive disorders, and olfactory dysfunctions) developed a previous mild form of COVID-19. Further studies are required to develop therapeutic strategies.Keywords: COVID 19, neuroCOVID, follow-up, cognitive disorders, neuropsychology, hypo/anosmia

Objectives Oral lichen planus with exclusive keratotic reticular, papular, and/or plaque-like lesions (K-OLP) is a clinical pattern of OLP that may be associated with a complex symptomatology and psychological alteration. The aim of the study was to evaluate the prevalence of anxiety (A) and depression (D) in patients with K-OLP, analyzing the potential predictors which can affect mental health status. Methods Three hundred K-OLP patients versus 300 healthy controls (HC) were recruited in 15 Italian universities. The Numeric Rating Scale (NRS), Total Pain Rating Index (T-PRI), and Hamilton Rating Scales for Depression and for Anxiety (HAM-D and HAM-A) were administered. Results The K-OLP patients showed statistically higher scores in the NRS, T-PRI, HAM-D, and HAM-A compared with the HC (p-value **). A and D were found in 158 (52.7%) and 148 (49.3%) K-OLP patients. Strong linear correlations were identified between HAM-A, HAM-D, NRS, T-PRI, and employment status and between HAM-D, HAM-A, NRS, T-PRI, employment status, and female gender. Multivariate logistic regression revealed that HAM-D and HAM-A showed the greatest increase in the R2 value for A and D in the K-OLP patients, respectively (DR2 = 55.5% p-value p-value Conclusions The prevalence of A and D is higher in the K-OLP patients compared with the HC, also found in K-OLP subjects without pain, suggesting that the processing of pain may be in a certain way independent of the processing of mood. Clinical relevance Mood disorders and pain assessment should be carefully performed in relation to K-OLP to obtain a complete analysis of the patients.

This project has received funding from the EU Horizon 2020 research and innovation programme under the ORCHESTRA project Grant Agreement No. 101016167, Collatuzzo G., De Palma G., Violante F.S., Porru S., Larese Filon F., Fabianova E., Violán C., Vimercati L., Leustean M., Rodriguez-Suarez M.M., Sansone E., Sala E., Zunarelli C., Lodi V., Monaco M.G.L., Spiteri G., Negro C., Beresova J., Carrasco-Ribelles L.A., Tafuri S., Asafo S.S., Ditano G., Abedini M., Boffetta P.

OBJECTIVE: Mammographic screening and management of breast cancer (BC) in elderly women are controversial and continue to be an important health problem. To investigate, through members of the Senologic International Society (SIS), the current global practices in BC in elderly women, highlighting topics of debate and suggesting perspectives. MATERIALS AND METHODS: The questionnaire was sent to the SIS network and included 55 questions on definitions of an elderly woman, BC epidemiology, screening, clinical and pathological characteristics, therapeutic management in elderly women, onco-geriatric assessment and perspectives. RESULTS: Twenty-eight respondents from 21 countries and six continents, representing a population of 2.86 billion, completed and submitted the survey. Most respondents considered women 70 years and older to be elderly. In most countries, BC was often diagnosed at an advanced stage compared to younger women, and age-related mortality was high. For this reason, participants recommended that personalized screening be continued in elderly women with a long life expectancy. In addition, this survey highlighted that geriatric frailty assessment tools and comprehensive geriatric evaluations needed to be used more and should be developed to avoid undertreatment. Similarly, multidisciplinary meetings dedicated to elderly women with BC should be encouraged to avoid under- and over-treatment and to increase their participation in clinical trials. CONCLUSION: Due to increased life expectancy, BC in elderly women will become a more important field in public health. Therefore, screening, personalized treatment, and comprehensive geriatric assessment should be the cornerstones of future practice to avoid the current excess of age-related mortality. This survey described, through members of the SIS, a global picture of current international practices in BC in elderly women.

Carasau bread is a flat bread, typical of Sardinia (Italy). The market of this food product has a large growth potential, and its industry is experiencing a revolution, characterized by digitalization and automation. To monitor the quality of this food product at different manufacturing stages, microwave sensors and devices could be a cost-effective solution. In this framework, knowledge of the microwave response of Carasau dough is required. Thus far, the analysis of the microwave response of Carasau doughs through dielectric spectroscopy has been limited to the dynamics of fermentation. In this work, we aim to perform complex dielectric permittivity measurements up to 8.5 GHz, investigating and modeling the role of water amount, salt and yeast concentrations on the spectra of this food product. A third-order Cole–Cole model was used to interpret the microwave response of the different samples, resulting in a maximum error of 1.58% and 1.60% for the real and imaginary parts of permittivity, respectively. Thermogravimetric analysis was also performed to support the microwave spectroscopy investigation. We found that dielectric properties of Carasau bread doughs strongly depend on the water content. The analysis highlighted that an increase in water quantity tends to increase the bounded water fraction at the expense of the free water fraction. In particular, the free water amount in the dough is not related to the broadening parameter γ2 of the second pole, whereas the bound water weight fraction is more evident in the γ2 and σdc parameters. An increase in electrical conductivity was observed for increasing water content. The microwave spectrum of the real part of the complex permittivity is slightly affected by composition, while large variation in the imaginary part of the complex dielectric permittivity can be identified, especially for frequencies below 4 GHz. The methodology and data proposed and reported in this work can be used to design a microwave sensor for retrieving the composition of Carasau bread doughs through their dielectric signature.

This project report describes the design and implementation of a system that measures blood oxygen saturation (SpO2) and heart rate (BPM) using the MAX30102 pulse oximeter and heart rate sensor module. The MAX30102 module is a highly sensitive and accurate sensor module that detects the light transmitted through the blood vessels in the fingertip to measure SpO2 and BPM. The hardware design of the system includes the MAX30102 module, an Arduino Uno board, and an OLED display. The MAX30102 module is connected to the Arduino Uno board through the I2C interface, and the OLED display is connected to the Arduino board through the SPI interface. The system is powered by a USB cable connected to a computer. To ensure that the MAX30102 module operates correctly, a voltage level converter is used to convert the 5V signals from the Arduino board to 3.3V signals that can be used by the MAX30102 module. The software design of the system includes a MAX30102 library and a main program written in Arduino IDE. The MAX30102 library is a set of functions that controls the MAX30102 module, including functions to initialize the module, configure the LEDs and photodetector, and read the raw data from the module. The library also includes functions to process the raw data and calculate the SpO2 and BPM values. The main program reads the raw data from the MAX30102 module and processes it using the functions provided by the MAX30102 library. The SpO2 and BPM values are then displayed on the OLED display. The paper concludes that the MAX30102 module is an effective and reliable sensor module for measuring SpO2 and BPM values and can be used in various health monitoring applications. The system can be further improved by integrating wireless communication modules, such as Bluetooth, to enable remote monitoring and data storage. Additionally, the MAX30102 module can be integrated into wearable devices for continuous health monitoring.

In this tutorial, we present a computational overview on computing Nash equilibria in Integer Programming Games ($IPG$s), $i.e.$, how to compute solutions for a class of non-cooperative and nonconvex games where each player solves a mixed-integer optimization problem. $IPG$s are a broad class of games extending the modeling power of mixed-integer optimization to multi-agent settings. This class of games includes, for instance, any finite game and any multi-agent extension of traditional combinatorial optimization problems. After providing some background motivation and context of applications, we systematically review and classify the state-of-the-art algorithms to compute Nash equilibria. We propose an essential taxonomy of the algorithmic ingredients needed to compute equilibria, and we describe the theoretical and practical challenges associated with equilibria computation. Finally, we quantitatively and qualitatively compare a sequential Stackelberg game with a simultaneous $IPG$ to highlight the different properties of their solutions., To appear in INFORMS TutORials in Operations Research 2023

The irrefutable benefits of physical activity as a tool for the prevention and treatment of several clinical conditions, including cardiovascular diseases, are nowadays widely recognized. However, physical exercise may trigger adverse events in subjects with underlying heart disease, often undiagnosed and asymptomatic. It is fundamental to consider that various sports disciplines have peculiar and specific physiological and metabolic adaptations, and it is essential to consider the individual profile of the subject, including gender. We report the case of an agonistic female swimmer with a history of tachycardia heartbeat when resurfacing from dynamic apnea, in whom a diagnosis of atrioventricular nodal reentrant tachycardia was made. This case report provides practical evidence of the importance of a personalized approach, in both individual sex- and sport-specific terms, to optimize the diagnostic and therapeutic pathways.

Pericardial effusion is a common finding in clinical practice either as incidental finding or manifestation of a systemic or cardiac disease. The spectrum of pericardial effusions ranges from mild asymptomatic effusions to cardiac tamponade. Etiology is one of the main factors determining patient's prognosis. However, in most cases the pericardial effusion, even if large, remains of unknown origin. Pectus excavatum (PEX) is a common deformity of the chest wall in which the inferior part of the sternum and the cartilage are displaced posteriorly. PEX is present within the first year of life in most affected children, more frequently in boys than girls. The chest deformity in PEX may lead to compression of the right-sided cavities between the sternum and the vertebral column impacting right ventricular anatomy and rendering cardiac assessment by echocardiography very difficult. The diagnosis of pericardial effusion is generally confirmed by echocardiography but determining its etiology may be difficult. Although many cases are idiopathic, a careful review of the patient's medical history, physical examination, and laboratory tests can reveal the etiology in most patients. The most common causes of pericardial effusion are infections, malignant tumors, connective tissue diseases, pericardial injury syndrome, myocardial pericardial disease, uremia. In the last years, an association between idiopathic pericardial effusion and PEX has been hypnotized. We report the cases of 2 athletes, 15 and 18 years old, who came to our attention for post COVID19 infection evaluation as indicated by ministerial "Return to Play" protocol. Physical examination was negative for any signs/symptoms. Resting ECG showed normal sinus rhythm. Stress test was performed and resulted negative for signs and symptoms of reduced coronary reserve and arrhythmias. The echocardiographic evaluation showed moderate-severe pericardial effusion, 20 mm and 18 mm, in the absence of hemodynamic alteration. Blood tests were performed (including CRP, ESR, blood count, D-Dimer, IL-6, uricemia) and resulted normal. CardioRM confirmed the presence of severe effusion without signs of hemodynamic impairment/instability. Holter-ECG, performed during training session, resulted negative for arrhythmic events. Athletes were followed up with six-monthly echocardiographic, HolterECG and stress test evaluations, with unchanged entity of the pericardial effusion and any arrythmia or symptoms at serial controls. Chronic pericardial effusion without active pericardial inflammation may represent a diagnostic and therapeutic challenge, especially in the later years as COVID-19 disease and vaccination may be associated with pericardial injury. In the last years, PEX has been associated with the finding of pericardial effusion. Although of interest, caution should be used before labeling indiscriminately a pericardial effusion as due to PEX, especially when clinical insights suggesting alternative diagnosis are present, such as neoplasm or tuberculosis, or when any signs of hemodynamic instability are present. On the contrary, when an otherwise idiopathic pericardial effusion is occasionally identified in a patient with PEX, both the patient and the referring physician may be reassured of the benign association of these two clinical entities, in the proper clinical setting.

We are recently faced with a progressive evolution of the therapeutic paradigm for radioiodine refractory differentiated thyroid cancer (RAI-R DTC), since the advent of tissue agnostic inhibitors. Thus, tumor genotype assessment is always more relevant and is playing a crucial role into clinical practice. We report the case of an elderly patient with advanced papillary thyroid carcinoma (PTC) harboring RET-CCDC6 fusion with four co-occurring mutations involving PI3KCA, TP53, and hTERT mutations, treated with pralsetinib under a compassionate use program. Despite the high histological grade and the coexistence of aggressive RET co-mutations, an impressive metabolic and structural tumor response has been obtained, together with a patient’s prolonged clinical benefit. A timely comprehensive molecular testing of those cases wild-type for the common thyroid carcinoma BRAF V600E-like and RAS-like driver mutations may uncover actionable gene rearrangements that can be targeted by highly selective inhibitors with great potential benefit for the patients.

In this short paper, we argue that the standard approach adopted by modern mixed-integer linear programming solvers of using very little cutting plane generation in the branch-and-bound tree can be too conservative and lead to the loss of significant opportunities. Our observation is motivated by some relatively simple computational investigation on a couple of instances in the MIPlib 2010 collection for which the benefit of generating globally valid cuts in the tree is significant. History: This “Challenge” paper was invited by the Editor-in-Chief and based on the topics raised by the author at his plenary address at the 2022 INFORMS Computing Society Conference in Tampa, Florida.

This study aims to find a correlation between bone marrow lesions (BMLs) in knee MRI and pathologies of joint structures. In addition, according to the six-letter system classification, the authors analyzed a potential association between the area affected by BMLs and the specific type of joint lesion.The authors screened all the knee MRIs performed in the investigation center between 2017 and 2018 to identify the presence of BMLs. The lesions were then categorized following the "six-letter system". The authors searched the presence of associated meniscal, chondral or ligamentous lesions. Finally, the authors researched a correlation between the lesion type described by the six-letter system classification and the associated lesions.MRI exams of 4000 patients were studied, identifying 666 BMLs. The associated lesions were collected for all patients, resulting in an overall prevalence of related lesions in almost 90% of patients. The authors found a statistical significance for type TLD (Tibia-Lateral-Articular) and ACL rupture. The study suggests a strong positive correlation between type E (Edge) and meniscal fracture or extrusion.BMLs in the knee are associated in 90% of cases with a radiological sign of related injury to the joint structures. The six-letter system of BMLs type TLD can be considered a sign of ACL rupture and type E as a high suspicious sign for meniscal extrusion. Those very typical BML patterns can help the clinician in the diagnosis of ACL tears and meniscal extrusion. Furthermore, the presence of a BML must be, for the clinician, a high suspicious sign of joint-related injuries.Level 1.

Background Throughout the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, healthcare workers (HCWs) have faced risk of infection from within the workplace via patients and staff as well as from the outside community, complicating our ability to resolve transmission chains in order to inform hospital infection control policy. Here we show how the incorporation of sequences from public genomic databases aided genomic surveillance early in the pandemic when circulating viral diversity was limited. Methods We sequenced a subset of discarded, diagnostic SARS-CoV-2 isolates between March and May 2020 from Boston Medical Center HCWs and combined this data set with publicly available sequences from the surrounding community deposited in GISAID with the goal of inferring specific transmission routes. Results Contextualizing our data with publicly available sequences reveals that 73% (95% confidence interval, 63%–84%) of coronavirus disease 2019 cases in HCWs are likely novel introductions rather than nosocomial spread. Conclusions We argue that introductions of SARS-CoV-2 into the hospital environment are frequent and that expanding public genomic surveillance can better aid infection control when determining routes of transmission.

Intestinal glucose absorption plays a central role in the regulation of glucose plasmatic; however, current clinical management does not target the gut for treating diabetes. This study evaluated the effects of peel and pulp aqueous extract from Hylocereus lemairei on human enterocytes under high glucose concentration. Anti-hyperglycemic and antiobesity activities in vitro were also evaluated. Extracts did not cause cytotoxicity at 1 to 500 μg/mL. Moreover, they were effective in attenuating oxidative stress (DCFH-DA assay) and inflammation (•ON production) caused by high glucose. Intestinal enzymes (α- glucosidase and pancreatic lipase) were inhibited by pulp and peel extracts (>60% and >95%, respectively). Extracts exhibited a redox capacity superior to ascorbic and chlorogenic acids, presenting high phenolic content, mainly anthocyanins. The main compounds for both extracts were chlorogenic acid and naringin, and peel stood both qualitatively and quantitatively. Data suggest red Pitaya has potential as a new medicine for diabetes.

People with HIV (PWH) who inject drugs often experience coexisting HIV- and substance use-related stigma manifestations. We assessed correlates of HIV stigma (Berger HIV stigma scale), substance use stigma (Substance Abuse Self-stigma scale) and intersectional HIV and substance use stigma in a cohort of PWH with a lifetime history of drug use in St. Petersburg, Russia. Intersectional stigma was defined as having a score greater than the median for both forms of stigma. Of the 208 participants, 56 (27%) had intersectional stigma. Depressive symptoms and alcohol dependence were significantly associated with a higher HIV and substance stigma score, but not with intersectional stigma. Individual and community interventions to reduce the impact of HIV stigma and substance use stigma affecting PWH who inject drugs should consider assessing and addressing mental health and unhealthy substance use. Further work with longitudinal data is needed to understand mechanisms leading to intersectional stigma.Las personas infectadas por el VIH que se inyectan drogas a menudo experimentan manifestaciones de estigma relacionadas con el uso de sustancias y el propio VIH. En este estudio evaluamos los correlatos de estigma asociado al VIH (escala de estigma asociado al VIH de Berger), el estigma asociado al uso de sustancias (“Substance Abuse Self-stigma Scale”) y el estigma interseccional del VIH y el uso de sustancias en una cohorte de personas infectadas por el VIH con antecedente de uso de drogas en San Petersburgo, Rusia. El estigma interseccional se definió como una puntuación superior a la mediana para ambas formas de estigma. De los 208 participantes, 56 (27%) tenían estigma interseccional. Los síntomas depresivos y la dependencia del alcohol se asociaron significativamente con una puntuación más alta de estigma relacionado con el VIH y las sustancias, pero no con el estigma interseccional. Las intervenciones individuales y comunitarias para reducir el impacto del estigma asociado al VIH y al uso de sustancias que afectan a las personas con VIH que se inyectan drogas deben tener en cuenta la salud mental y el uso nocivo de sustancias. Se necesitan estudios con datos longitudinales para comprender mejor los mecanismos que conducen al estigma interseccional.