Introduction: Treatment is generally not available for drug-induced liver injury (DILI) patients except in some specific circumstances. The management of DILI is based on the withdrawal of the responsible drug and monitoring the patients and only a few patients need to be referred to a transplant center. Some studies on the role of ursodeoxycholic acid (UDCA) in DILI have been published. The aim of this study was to perform a systematic review of the role of UDCA in the treatment and prevention of DILI. Methods: A search was undertaken in PubMed, with the key words ursodeoxycholic acid, drug-induced liver injury and hepatotoxicity following the PRISMA guidelines. Results: A total of 33 publications were identified: 25 case reports and 8 case series. In 18 of the 25 cases reports (22 patients), authors reported improvement of liver injury associated with UDCA therapy whereas 7 case reports did not show clinical or biochemical improvement after UDCA treatment. There were 4 studies evaluating the role of UDCA in the treatment of DILI, three prospective (one being a clinical trial) and one retrospective studies. Three studies observed liver profile improvements associated with UDCA. In addition, four studies evaluated UDCA in the prevention of DILI: one pilot study, two randomized clinical trials (RCT) and one retrospective study. Three of these studies observed a lower percentage of patients with an increase in transaminases in the groups that used UDCA for DILI prevention. Conclusion: According to available data UDCA seems to have some benefits in the treatment and prevention of DILI. However, the design of the published studies does not allow a firm conclusion to be drawn on the efficacy of UDCA in DILI. A well designed RCT to evaluate the role of UDCA in DILI is needed.

As tecnologias modernas convencionais de produção de manga são muito importantes para o crescimento da produção mundial, mas a maioria não é aceita nos sistemas orgânicos. Dessa forma, esse trabalho de revisão de literatura descreve práticas viáveis de transição orgânica em contraponto às modernas técnicas do manejo conservador com o objetivo de avaliar a importância do manejo alternativo na produção sustentável em manga buscando eliminar o uso de agroquímicos sintéticos e produzir frutos orgânicos com melhor aceitação comercial. A manga é bastante consumida no mundo, e o Brasil é um dos principais produtores e exportadores, mas a maior parte da produção se encontra, principalmente, no Submédio do Vale do São Francisco e em São Paulo, mantendo supremacia no manejo convencional, que apesar de ser bastante produtivo, ainda adota práticas insustentáveis que promovem a degradação ambiental, como o uso maciço de agrotóxicos. Devido à cobrança dos consumidores e ambientalistas a produção orgânica vem ganhando espaço, com práticas de fertilização orgânica, policultivos, adubação verde, consorciação de cultivos, entre outras, buscando desenvolver a agrobiodiversidade e favorecer o controle biológico, para produzir frutos seguros e ambientalmente corretos, atendendo aos pré-requisitos econômicos, ambientais, sociais e culturais. Práticas indispensáveis à transição do sistema convencional para o agroecológico, que apesar de crescente em todo o mundo, encontram dificuldades de expansão, principalmente em cultivos perenes, devido à falta de apoio público institucional, assistência técnica, insumos disponíveis e pesquisas de apoio, essenciais ao incremento produtivo orgânico e/ou agroecológico.

Although high and simulated altitude training has become an increasingly popular training method, no study has investigated the influence of acute hypoxic exposure on balance in team-sport athletes. Therefore, the purpose of this study was to investigate whether acute exposure to normobaric hypoxia is detrimental to balance performance in highly-trained basketball players. Nine elite and nine sub-elite male basketball players participated in a randomized, single-blinded, cross-over study. Subjects performed repeated trials of a single-leg balance test (SLBT) in an altitude chamber in normoxia (NOR; approximately sea level) with FiO2 20.9% and PiO2 ranging from 146.7 to 150.4 mmHg and in normobaric hypoxia (HYP; ~3,800 m above sea level) with FiO2 13.0% and PiO2 ranging from 90.9 to 94.6 mmHg. The SLBT was performed three times: 15 min after entering the environmental chamber in NOR or HYP, then two times more interspersed by 3-min rest. Peripheral oxygen saturation (SpO2) and heart rate (HR) were recorded at four time points: after the initial 15-min rest inside the chamber and immediately after each SLBT. Across the cohort, the balance performance was 7.1% better during NOR than HYP (P < 0.01, ηp2 = 0.58). However, the performance of the elite group was not impaired by HYP, whereas the sub-elite group performed worse in the HYP condition on both legs (DL: P = 0.02, d = 1.23; NDL: P = 0.01, d = 1.43). SpO2 was lower in HYP than NOR (P < 0.001, ηp2 = 0.99) with a significant decline over time during HYP. HR was higher in HYP than NOR (P = 0.04, ηp2 = 0.25) with a significant increase over time. Acute exposure to normobaric hypoxia detrimentally affected the balance performance in sub-elite but not elite basketball players.

Conventional ophthalmic dosage forms, although being simple to apply and presenting great patients' compliance, display poorer drug bioavailability and retention time on the eye surface. To cope with these problems, one must formulate novel drug delivery systems, such as nanosystems, for ocular drug delivery. Different formulation methods of nanoparticles have been developed, but some of them, such as the supercritical fluid method, have not reached their full potential in ocular drug delivery. This article aims to present the possibilities of the supercritical fluid method when preparing nanosystems for ocular drug delivery. This method could be used more frequently and efficiently because it is environmentally friendly and produces nanoparticles of the desired physicochemical properties, which is especially important in ocular drug delivery considering its peculiarities. Modifications of the supercritical fluid method can be used when a drug has some specific properties, which is an additional benefit in ocular drug delivery.

This study aimed to generate a linguistic equivalent of the COVID Stress Scales (CSS) in the Serbian language and examine its psychometric characteristics. Data were collected from September to December 2020 among the general population of three cities in Republic of Serbia and Republic of Srpska, countries where the Serbian language is spoken. Participants completed a socio-demographic questionnaire, followed by the CSS and Perceived Stress Scale (PSS). The CSS was validated using the standard methodology (i.e., forward and backward translations, pilot testing). The reliability of the Serbian CSS was assessed using Cronbach’s alpha and McDonald’s omega coefficients and convergent validity was evaluated by correlating the CSS with PSS. Confirmatory factor analysis was performed to examine the construct validity of the Serbian CSS. This study included 961 persons (52.8% males and 47.2% females). The Cronbach’s alpha coefficient of the Serbian CSS was 0.964 and McDonald’s omega was 0.964. The Serbian CSS with 36 items and a six-factorial structure showed a measurement model with a satisfactory fit for our population (CMIN/DF = 4.391; GFI = 0.991; RMSEA = 0.025). The CSS total and all domain scores significantly positively correlated with PSS total score. The Serbian version of the CSS is a valid and reliable questionnaire that can be used in assessing COVID-19-related distress experienced by Serbian speaking people during the COVID-19 pandemic as well as future epidemics and pandemics.

Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study, integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2 positive, 94 were symptomatic and 2 died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies and 82% had neutralizing antibodies against wild type SARS-CoV-2, whereas neutralizing antibody titers against the Alpha, Beta and Delta variants were substantially reduced. S1-reactive antibody levels decreased in 13% of patients, whereas neutralizing antibody titers remained stable for up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment specific, but presented compensatory cellular responses, further supported by clinical recovery in all but one patient. Overall, these findings advance the understanding of the nature and duration of the immune response to SARS-CoV-2 in patients with cancer.

Lung cancer is the leading cause of cancer-related deaths worldwide. Despite growing efforts for its early detection by screening populations at risk, the majority of lung cancer patients are still diagnosed in an advanced stage. The management of lung cancer has dramatically improved in the last decade and is no longer based on the “one-fits-all” paradigm or the general histological classification of non-small cell versus small cell lung cancer. Emerging options of targeted therapies and immunotherapies have shifted the management of lung cancer to a more personalized treatment approach, significantly influencing the clinical course and outcome of the disease. Molecular biomarkers have emerged as valuable tools in the prognosis and prediction of therapy response. In this review, we discuss the relevant biomarkers used in the clinical management of lung tumors, from diagnosis to prognosis. We also discuss promising new biomarkers, focusing on non-small cell lung cancer as the most abundant type of lung cancer.

People living with HIV (PLWH) are at higher risk of poorer COVID‐19 outcomes. Vaccination is a safe and effective method of prevention against many infectious diseases, including COVID‐19. Here we investigate the strategies for national COVID‐19 vaccination programmes across central and eastern Europe and the inclusion of PLWH in vaccination programmes.

Atrial flutter (AFL) is a common atrial arrhythmia typically characterized by electrical activity propagating around specific anatomical regions. It is usually treated with catheter ablation. However, the identification of rotational activities is not straightforward, and requires an intense effort during the first phase of the electrophysiological (EP) study, i.e., the mapping phase, in which an anatomical 3D model is built and electrograms (EGMs) are recorded. In this study, we modeled the electrical propagation pattern of AFL (measured during mapping) using network theory (NT), a well-known field of research from the computer science domain. The main advantage of NT is the large number of available algorithms that can efficiently analyze the network. Using directed network mapping, we employed a cycle-finding algorithm to detect all cycles in the network, resembling the main propagation pattern of AFL. The method was tested on two subjects in sinus rhythm, six in an experimental model of in-silico simulations, and 10 subjects diagnosed with AFL who underwent a catheter ablation. The algorithm correctly detected the electrical propagation of both sinus rhythm cases and in-silico simulations. Regarding the AFL cases, arrhythmia mechanisms were either totally or partially identified in most of the cases (8 out of 10), i.e., cycles around the mitral valve, tricuspid valve and figure-of-eight reentries. The other two cases presented a poor mapping quality or a major complexity related to previous ablations, large areas of fibrotic tissue, etc. Directed network mapping represents an innovative tool that showed promising results in identifying AFL mechanisms in an automatic fashion. Further investigations are needed to assess the reliability of the method in different clinical scenarios.

We investigate the scattering attenuation characteristics of the Martian crust and uppermost mantle to understand the structure of the Martian interior. We examine the energy decay of the spectral envelopes for 21 high-quality Martian seismic events from Sol 128 to Sol 500 of InSight operations. We use the model of Dainty et al. (1974b) to approximate the behavior of energy envelopes resulting from scattered wave propagation through a single diffusive layer over an elastic half-space. Using a grid search, we mapped the layer parameters that fit the observed InSight data envelopes. The single diffusive layer model provided better fits to the observed energy envelopes for High Frequency (HF) and Very High Frequency (VF) than for the Low Frequency (LF) and Broadband (BB) events. This result is consistent with the suggested source depths (Giardini et al., 2020) for these families of events and their expected interaction with a shallow scattering layer. The shapes of the observed data envelopes do not show a consistent pattern with event distance, suggesting that the diffusivity and scattering layer thickness is non-uniform in the vicinity of InSight at Mars. Given the consistency in the envelope shapes between HF and VF events across epicentral distances and the tradeoffs between the parameters that control scattering, the dimensions of the scattering layer remain unconstrained but require that scattering strength decreases with depth and that the rate of decay in scattering strength is fastest near the surface. This is generally consistent with the processes that would form scattering structures in planetary lithospheres.

Introduction: There is limited knowledge on the sensitization patterns to peanut proteins and food allergy in the Middle East. The objective of this study is to analyze the relationship between sensitization patterns to peanut proteins and clinical symptoms in a group of patients with physician-diagnosed peanut allergy (PA) in Kuwait. Methods: PA patients were evaluated by the skin prick test (SPT), serum total IgE, peanut-specific IgE (sIgE), and sIgE against Ara h 1–3, 8, and 9, and clinical data were collected. Results: Sixty-nine patients were included. A positive correlation between peanut SPT and sIgE was detected for all 3 storage proteins (Ara h 1–3) in patients <6 years old and for Ara h 1 and 2 in older patients. ROC analysis of positive correlations showed that oral food challenge should be considered for definite diagnosis of PA only if the level of Ara h 2 is <22.25 KUA/L, with level of Ara h 2 ≥15.4 allowing the detection of systemic reactions with a sensitivity of 55.56%. Patients presenting with systemic reactions more frequently had positive Ara h 1 (88.9%) and Ara h 2 (83.3%), compared with 44.1% and 52.9% in those with local reaction (p = 0.0046 and p = 0.0378). The levels of Ara h 1 and 2 were also significantly higher in patients with systemic reactions compared to those with a local reaction, with those differences being especially relevant for Ara h 2 (15.9 vs. 0.4) (p = 0.0005). Conclusions: The pattern of sensitization to peanut proteins in the Middle East is similar to that of the Western world. Measurement of sIgE antibodies to Ara h 1, 2, and 3 is useful in the diagnosis of PA and in the investigation of reactions to raw and roasted peanuts.

Selecting the optimal binder and the sorbent affinity for selected compounds can cause the composite to behave either as an efficient extraction coating, as a permeable membrane, or as an impermeable barrier. If the compound partitions onto the sorbent with high preference, it becomes stationary and the composite behaves as an impermeable barrier, while appropriately optimized affinity will result in effective permeation. To understand this phenomenon, we utilize solid-phase microextraction to characterize the mass transfer attributes of different separation composites. Our results indicate that for strong sorbents, the extraction rate is primarily controlled by the diffusion in the extraction phase rather than the sample matrix, even if it is relatively thin. Low analyte diffusion is caused by the retarding force generated by the partitioning of analytes into the sorbent, as migration through the composite is driven by the unbound form of the compound in the binder. One of the main contributions of this work is that an understanding of the extraction composite parameters that control mass transfer during extraction enables better optimization of binder/sorbent extraction phase composition for a given application. Another contribution of this work shows how a heterogeneous coating model can be simplified into a homogeneous coating model. The developed models enable an enhanced understanding of mass transfer kinetics, and they provide insight into how to optimize the extraction phase parameters for a given method involving sorbent particles in polymeric media, including membranes and paints, in addition to extraction coatings.

Background Recent research has closely linked adipocytokines to liver inflammation and fibrosis progression in patients with non-alcoholic liver disease. This study aimed to determine the relationship of serum adiponectin and resistin levels with the severity of liver fibrosis in patients with chronic hepatitis B (CHB), depending on the duration of antiviral therapy. Methods The cross-sectional study included 75 patients with CHB divided into two groups: the T1 group (undergoing antiviral therapy for up to 2 years) and the T2 group (undergoing antiviral therapy over 2 years). The control group consisted of 40 healthy people. Serum concentrations of adiponectin and resistin were estimated with the ELISA method, while the degree of liver fibrosis was determined using FIB-4 and APRI score. Results There were no statistically significant differences in the mean serum adiponectin levels in relation to the duration of antiviral therapy. Higher values of serum resistin concentration were confirmed in patients of the T1 group compared to healthy controls (p=0.001) and to the T2 group (p=0.031). The mean level of serum resistin concentration was significantly higher in the group of patients with a higher FIB-4 score (9.12±3.39 vs 5.58±3.36 ng/mL, p=0.001) and higher APRI score (17.45±3.96 ng/mL vs 4.82±1.11 ng/mL, p=0.001). A positive correlation was found between serum resistin levels and the degree of liver fibrosis (p<0.001). There was no significant difference between mean serum adiponectin levels according to the values of FIB-4 and APRI scores. Conclusions Progression of liver fibrosis estimated by FIB4 and APRI scores as well as the length of antiviral treatment had a significant effect on serum resistin values in CHB patients on antiviral therapy.

Disposal of healthcare waste is a key issue of environmental sustainability in the world. The amount of healthcare waste is increasing every day, and it is necessary to adequately dispose of this kind of waste. There are various treatments for healthcare waste disposal, of which incineration of healthcare waste is one of the solutions. This paper suggests a model for selection of the type of incinerators that best solve the problem of healthcare waste in secondary healthcare institutions in Bosnia and Herzegovina. In the selection of incinerators, extended sustainability criteria were applied. Basic sustainability criteria: environmental, economic, and social criteria, were extended with the technical criterion. To assess which of the incinerators best meets the needs for healthcare waste collection, multi-criteria decision-making was used. For this purpose, a combination of two MCDA methods was applied in this paper, namely full consistency method (FUCOM) and compromise ranking of alternatives from distance to ideal solution (CRADIS). The FUCOM method was applied to determine the weights of the criteria, while the CRADIS method was applied to rank the alternatives. The best alternative of the six alternatives used is A2 (I8-M50), followed by alternative A1 (I8-M40), while the worst ranked alternative is A5 (I8-M100). These results were confirmed by applying the other six methods of multi-criteria analysis and the performed sensitivity analysis. The contribution of this paper is reflected through a new method of multi-criteria analysis that was used to solve decision-making problems. This method has shown simplicity and flexibility in operation and can be used in all problems when it is necessary to make a multi-criteria selection of alternatives.

Machine learning algorithms have been drawing attention in lung disease research. However, due to their algorithmic learning complexity and the variability of their architecture, there is an ongoing need to analyze their performance. This study reviews the input parameters and the performance of machine learning applied to diagnosis of chronic obstructive pulmonary disease (COPD). One research focus of this study was on clearly identifying problems and issues related to the implementation of machine learning in clinical studies. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) protocol, 179, 1032, and 36,500 titles were identified from the PubMed, Scopus, and Google Scholar databases respectively. Studies that used machine learning to detect COPD and provided performance measures were included in our analysis. In the final analysis, 24 studies were included. The analysis of machine learning methods to detect COPD reveals the limited usage of the methods and the lack of standards that hinder the implementation of machine learning in clinical applications. The performance of machine learning for diagnosis of COPD was considered satisfactory for several studies; however, given the limitations indicated in our study, further studies are warranted to extend the potential use of machine learning to clinical settings.