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Abstract High lipoprotein(a) (Lp(a)) levels are associated with an increased risk of arterial hypertension (AHT) and atherosclerotic cardiovascular disease. However, little is known about the detailed profile of AHT based on Lp(a) levels. This observational study focused on elucidating the relationship between Lp(a) concentrations and specific indices obtained from 24-h ambulatory blood pressure (BP) monitoring in hypertensive patients over 18 years of age. We gathered and analyzed data on BP indices along with demographic, epidemiological, clinical, and laboratory variables from 227 hypertensive patients, median age 56 years, including 127 women (56%). After comparing hypertensive patients with Lp(a) levels above and below 125 nmol/L, we found that a 10 mmHg increase in nocturnal systolic BP and all pulse pressure indices (24-h, daytime, and night-time) was associated with an increased risk of high Lp(a) levels by more than 20% and 40%, respectively. Similarly, each 10% increase in the area under the function over time of nocturnal diastolic BP dipping was associated with more than a 30% decrease in the odds of belonging to the elevated Lp(a) levels category. Additionally, Lp(a) levels above 125 nmol/L were associated with higher 24-h, daytime, and night-time systolic BP and pulse pressure load. The relationship between Lp(a) and AHT appears to extend beyond conventional BP measurements, which may be relevant given the prognostic implications of nocturnal BP and pulse pressure indices.

With the ever-increasing influence of machine learning models, it has become necessary to explain their predictions. The SHAP framework provides a solution to this problem by assigning a score to each feature of a model such that it reflects the feature contribution to the prediction. Although SHAP is widely used, it is hampered by its computational cost when preserving model-agnosticism. This paper proposes a model-agnostic algorithm, TopShap, to efficiently approximate the SHAP values of the top-k most important features. TopShap uses confidence interval bounds of the approximate SHAP values to determine on the fly which features can no longer be part of the top-k and then removes them from the computation, thus saving computational resources. This cost reduction makes TopShap better suited than competing model-agnostic methods for top-k SHAP value computation. The evaluation of TopShap shows that it performs efficient pruning of the feature search space, in turn leading to a substantial reduction in the execution time when compared to the existing most efficient agnostic approach, Kernel SHAP. The experiments presented in this work cover a wide range of numbers of features and instances, using the following public datasets: Concrete, Wine quality, Appliances energy, PBMC gene expression, Mercedes, CT locations, and a synthetic regression. Various models were used to demonstrate model-agnosticism: Regression Forest, Multi-Layer Perceptron, RBF-kernel Support Vector Regression, and Stacked Generalization.

In 2019, the Recommendations for the management of patients with lung cancer were published bringing much-needed standardisation of diagnosis and treatment to improve survival of patients with lung cancer. Three years after the original Recommendations were published, the update of the Recommendations brings the most innovations in the chapter on systemic treatment of patients with lung cancer. This reflects the remarkable progress made in the field of understanding the oncogenesis and biology of lung cancer and thus the development of new drugs. The burden of lung cancer remains high, as lung cancer is still the most common cause of cancer related death in our country and worldwide. Lung cancer is responsible for one of five cancer-related deaths. Almost one third of patients with lung cancer do not receive any oncological treatment, either because of poor performance status, comorbidities or the extent of the disease. Half of the patients have metastatic disease at diagnosis, resulting in only small improvements in survival despite advances in the treatment of lung cancer patients. These data remind us that if we are to make major shifts in the management of lung cancer patients, we will need to take different approaches. The most promising seems to be the detection of early stages of lung cancer which offers the best treatment results. The Recommendations written here are guidelines for the management of patients with lung cancer. Only with comprehensive multidisciplinary treatment approach, the best outcome from the prognostically unfavourable disease can be offered.

Pandemija virusa SARS-CoV-2 je popolnoma presenetila celotni svet. V zelo kratkem času je bilo potrebno reorganizirati zdravstveni sistem v celoti. Bolnišnice, ki sprejemajo bolnike s covidom-19, je bilo treba čez noč prestrukturirati v del bolnišnice za bolnike s covidom-19 in v del bolnišnice z ostalimi bolniki, ki nimajo covida-19. Pri delu s kirurškim bolnikom s covidom-19 je potrebna predvsem popolna in dosledna uporaba zaščitnih sredstev, da ne pride do okužbe zdravstvenega osebja. Prav tako je potrebna posebna klinična pot znotraj bolnišnic, da ne pride do kontaminacije v delu bolnišnice, ki je brez bolnikov s covidom-19. Začasno so bile odpovedane vse elektivne kirurške obravnave. Zdaj se pod posebnimi pogoji za zaščito zdravstvenih delavcev in bolnikov ponovno sproščajo. Pred elektivnimi kirurškimi posegi se priporoča jemanje brisov na covid-19, vendar to ni nujno. Brisi so namreč v 30 % negativni oz. nezanesljivi in se nanje ne moremo popolnoma zanesti. Predvsem je pomembno, da bolnik v zadnjih 14 dneh ni imel znakov prehladne bolezni in prav tako ne člani njegove družine. Znotraj ustanove se moramo vesti do vsakega sprejetega bolnika, kot da je lahko okužen z virusom SARS-CoV-2. Enako velja za osebje. Ravnati se je potrebno glede zaščitnih ukrepov tako, kot da je vsak od zaposlenih okužen z virusom SARS-CoV-2.

We aimed to evaluate the correlation of plasma levels of thiobarbituric acid reactive substances (TBARS) and reduced thiols with morbidity, mortality and immune response during and after SARS-CoV-2 infection. This was an observational study that included inpatients with SARS-CoV-2 infection older than 65 years. The individuals were followed up to the twelfth month post-discharge. Plasma levels of TBARS and reduced thiols were quantified as a measure of lipid and protein oxidation, respectively. Fatal and non-fatal events were evaluated during admission and at the third, sixth and twelfth month post-discharge. Differences in oxidative stress markers between the groups of interest, time to a negative RT-qPCR and time to significant anti-SARS-CoV-2 IgM titers were assessed. We included 61 patients (57% women) with a mean age of 83 years old. After multivariate analysis, we found differences in TBARS and reduced thiol levels between the comparison groups in fatal and non-fatal events during hospital admission. TBARS levels were also correlated with fatal events at the 6th and 12th months post-discharge. One year after hospital discharge, other predictors rather than oxidative stress markers were relevant in the models. The median time to reach significant anti-SARS-CoV-2 IgM titers was lower in patients with low levels of reduced thiols. Assessment of some parameters related to oxidative stress may help identify groups of patients with a higher risk of morbidity, mortality and delayed immune response during and after SARS-CoV-2 infection.

As in other fields, chronotherapy applied to arterial hypertension (AHT) may have implications on oxidative stress. We compared the levels of some redox markers between hypertensive patients with morning and bedtime use of renin-angiotensin-aldosterone system (RAAS) blockers. This was an observational study that included patients older than 18 years with a diagnosis of essential AHT. Blood pressure (BP) figures were measured using twenty-four-hour ambulatory BP monitoring (24-h ABPM). Lipid peroxidation and protein oxidation were assessed using the thiobarbituric acid reactive substances (TBARS) and reduced thiols assays. We recruited 70 patients with a median age of 54 years, of whom 38 (54%) were women. In hypertensive patients with bedtime use of RAAS blockers, reduced thiol levels showed a positive correlation with nocturnal diastolic BP decrease. TBARS levels were associated with bedtime use of RAAS blockers in dipper and non-dipper hypertensive patients. In non-dipper patients, bedtime use of RAAS blockers was also associated with a decrease in nocturnal diastolic BP. Chronotherapy applied to bedtime use of some BP-lowering drugs in hypertensive patients may be linked to a better redox profile.

An impaired nocturnal decrease in diastolic blood pressure (DBP) increases the blood pressure (BP) load, which is a main factor in endothelial dysfunction, atherosclerosis, and arterial stiffness. We aimed to quantify some markers of oxidative stress in hypertensive patients, to compare their levels between individuals with dipper and non-dipper DBP profiles, and to assess their correlation with the nocturnal DBP (nDBP) dipping. It was an observational study that included patients older than 18 years with a diagnosis of essential hypertension who consented to participate. The collected variables were some indices of 24-h ambulatory blood pressure monitoring, demographic, epidemiological, clinical, and laboratory variables. Plasma thiobarbituric acid reactive substances (TBARS) and reduced thiols, together with serum vitamin E, vitamin A, copper (Cu), and zinc (Zn) levels were assessed as oxidative stress markers. We recruited 248 patients with a median age of 56 years (56% women). The percentage of nDBP dipping showed a weak positive correlation with reduced thiol, vitamin E, and vitamin A levels; and a weak negative correlation with Cu levels. We also found a negative correlation between nDBP dipping and the TBARS/Thiol, TBARS/Vitamin E, and TBARS/Vitamin A ratios. After multivariate analysis, we found that increased TBARS/Thiol ratio and serum Cu levels were associated with a higher risk of a non-dipper DBP profile. As in other situations of increased cardiovascular risk, an impaired nDBP decrease may coincide with abnormalities in redox status.

Projection neurons (PNs) in the mammalian olfactory bulb (OB) receive input from the nose and project to diverse cortical and subcortical areas. Morphological and physiological studies have highlighted functional heterogeneity, yet no molecular markers have been described that delineate PN subtypes. Here, we used viral injections into olfactory cortex and fluorescent nucleus sorting to enrich PNs for high-throughput single nucleus and bulk RNA deep sequencing. Transcriptome analysis and RNA in situ hybridization identified distinct mitral and tufted cell populations with characteristic transcription factor network topology, cell adhesion, and excitability-related gene expression. Finally, we describe a new computational approach for integrating bulk and snRNA-seq data and provide evidence that different mitral cell populations preferentially project to different target regions. Together, we have identified potential molecular and gene regulatory mechanisms underlying PN diversity and provide new molecular entry points into studying the diverse functional roles of mitral and tufted cell subtypes.

No abstract.

Rak požiralnika je razmeroma redek tumor z veliko umrljivostjo. Pogosteje zbolijo moški v 6. ali 7. desetletju življenja. V zadnjih letih v zahodnem svetu opažamo stalen porast incidence adenokarcinoma distalnega požiralnika in ezofagogastričnega stika (EGS). Vzrok je najverjetneje posledica spremenjenega načina življenja s povišano incidenco debelosti in gastroezofagealne refluksne bolezni. Nova, 7. Revizija TNM klasifikacije, uvršča rak požiralnika in EGS skupaj pod rak požiralnika. Pri izbrani skupini bolnikov je bolezen ozdravljiva, vendar je zdravljenje dolgotrajno, praviloma kombinirano in z visoko morbiditeto, ki lahko precej zmanjša kakovost bolnikovega življenja. Zaradi specifične anatomije rak požiralnika in EGS zgodaj zaseva in je zato v primerjavi z ostalimi malignomi prebavil prognostično slabši.

Insects determine their body segments in two different ways. Short-germband insects, such as the flour beetle Tribolium castaneum, use a molecular clock to establish segments sequentially. In contrast, long-germband insects, such as the vinegar fly Drosophila melanogaster, determine all segments simultaneously through a hierarchical cascade of gene regulation. Gap genes constitute the first layer of the Drosophila segmentation gene hierarchy, downstream of maternal gradients such as that of Caudal (Cad). We use data-driven mathematical modelling and phase space analysis to show that shifting gap domains in the posterior half of the Drosophila embryo are an emergent property of a robust damped oscillator mechanism, suggesting that the regulatory dynamics underlying long- and short-germband segmentation are much more similar than previously thought. In Tribolium, Cad has been proposed to modulate the frequency of the segmentation oscillator. Surprisingly, our simulations and experiments show that the shift rate of posterior gap domains is independent of maternal Cad levels in Drosophila. Our results suggest a novel evolutionary scenario for the short- to long-germband transition and help explain why this transition occurred convergently multiple times during the radiation of the holometabolan insects.

Malignant pleural effusion (MPE) is an exudative effusion with malignant cells. MPE is a common symptom and accompanying manifestation of metastatic disease. It affects up to 15% of all patients with cancer and is the most common in lung, breast cancer, lymphoma, gynecological malignancies and malignant mesothelioma. In the last year, many studies were performed focusing on the pathophysiological mechanisms of MPE. With the advancement in molecular techniques, the importance of tumor-host cell interactions is becoming more apparent. Additionally, the process of pathogenesis is greatly affected by activating mutations of EGFR, KRAS, PIK3CA, BRAF, MET, EML4/ALK and RET, which correlate with an increased incidence of MPE. Considering all these changes, the authors aim to present a literature review of the newest findings, review of the guidelines and pathophysiological novelties in this field. Review of the just recently, after seven years published, practice guidelines, as well as analysis of more than 70 articles from the Pubmed, Medline databases that were almost exclusively published in indexed journals in the last few years, have relevance and contribute to the better understanding of the presented topic. MPE still presents a severe medical condition in patients with advanced malignancy. Recent findings in the field of pathophysiological mechanisms of MPE emphasize the role of molecular factors and mutations in the dynamics of the disease and its prognosis. Treatment guidelines offer a patient-centric approach with the use of new scoring systems, an out of hospital approach and ultrasound. The current guidelines address multiple areas of interest bring novelties in the form of validated prediction tools and can, based on evidence, improve patient outcomes. However, the role of biomarkers in a clinical setting, possible new treatment modalities and certain specific situations still present a challenge for new research.

Pattern formation during development is a highly dynamic process. In spite of this, few experimental and modelling approaches take into account the explicit time-dependence of the rules governing regulatory systems. We address this problem by studying dynamic morphogen interpretation by the gap gene network in Drosophila melanogaster. Gap genes are involved in segment determination during early embryogenesis. They are activated by maternal morphogen gradients encoded by bicoid (bcd) and caudal (cad). These gradients decay at the same time-scale as the establishment of the antero-posterior gap gene pattern. We use a reverse-engineering approach, based on data-driven regulatory models called gene circuits, to isolate and characterise the explicitly time-dependent effects of changing morphogen concentrations on gap gene regulation. To achieve this, we simulate the system in the presence and absence of dynamic gradient decay. Comparison between these simulations reveals that maternal morphogen decay controls the timing and limits the rate of gap gene expression. In the anterior of the embyro, it affects peak expression and leads to the establishment of smooth spatial boundaries between gap domains. In the posterior of the embryo, it causes a progressive slow-down in the rate of gap domain shifts, which is necessary to correctly position domain boundaries and to stabilise the spatial gap gene expression pattern. We use a newly developed method for the analysis of transient dynamics in non-autonomous (time-variable) systems to understand the regulatory causes of these effects. By providing a rigorous mechanistic explanation for the role of maternal gradient decay in gap gene regulation, our study demonstrates that such analyses are feasible and reveal important aspects of dynamic gene regulation which would have been missed by a traditional steady-state approach. More generally, it highlights the importance of transient dynamics for understanding complex regulatory processes in development.

Prvi cilji zdravljenja simptomatskih malignomov požiralnika vključujejo vzdrževanje prehranske poti, preprečevanje krvavitev in bolečin. Vsi bolniki potrebujejo multidisciplinarno oceno, da jim zagotovimo primerno, običajno več-modalno terapijo. Opredelitev najbolj ustreznega načina prehranske podpore bolnika z rakom požiralnika mora biti individualna. Zdravljenje je odvisno od stadija bolezni, simptomov, razpoložljive tehnologije in izkušenj lečečega zdravnika. Predstavljamo naš način reševanja disfagije s pomočjo znotraj- -lumenskih opornic požiralnika. V naši praksi se je znotraj- -lumenska opornica požiralnika pokazala za zelo učinkovit in bolniku najprijaznejši način zagotavljanja optimalnega vnosa hranil pred ter med neoadjuvantno terapijo. Zapletov je malo, vstavitve pa nimajo negativnega vpliva na perioperativne izide.

The segmentation gene network in insects can produce equivalent phenotypic outputs despite differences in upstream regulatory inputs between species. We investigate the mechanistic basis of this phenomenon through a systems-level analysis of the gap gene network in the scuttle fly Megaselia abdita (Phoridae). It combines quantification of gene expression at high spatio-temporal resolution with systematic knock-downs by RNA interference (RNAi). Initiation and dynamics of gap gene expression differ markedly between M. abdita and Drosophila melanogaster, while the output of the system converges to equivalent patterns at the end of the blastoderm stage. Although the qualitative structure of the gap gene network is conserved, there are differences in the strength of regulatory interactions between species. We term such network rewiring ‘quantitative system drift’. It provides a mechanistic explanation for the developmental hourglass model in the dipteran lineage. Quantitative system drift is likely to be a widespread mechanism for developmental evolution.

Efficient network inference is one of the challenges of current-day biology. Its application to the study of development has seen noteworthy success, yet a multicellular context, tissue growth, and cellular rearrangements impose additional computational costs and prohibit a wide application of current methods. Therefore, reducing computational cost and providing quick feedback at intermediate stages are desirable features for network inference. Here we propose a hybrid approach composed of two stages: exploration with scatter search and exploitation of intermediate solutions with low temperature simulated annealing. We test the approach on the well-understood process of early body plan development in flies, focusing on the gap gene network. We compare the hybrid approach to simulated annealing, a method of network inference with a proven track record. We find that scatter search performs well at exploring parameter space and that low temperature simulated annealing refines the intermediate results into excellent model fits. From this we conclude that for poorly-studied developmental systems, scatter search is a valuable tool for exploration and accelerates the elucidation of gene regulatory networks.

Understanding the function and evolution of developmental regulatory networks requires the characterisation and quantification of spatio-temporal gene expression patterns across a range of systems and species. However, most high-throughput methods to measure the dynamics of gene expression do not preserve the detailed spatial information needed in this context. For this reason, quantification methods based on image bioinformatics have become increasingly important over the past few years. Most available approaches in this field either focus on the detailed and accurate quantification of a small set of gene expression patterns, or attempt high-throughput analysis of spatial expression through binary pattern extraction and large-scale analysis of the resulting datasets. Here we present a robust, "medium-throughput" pipeline to process in situ hybridisation patterns from embryos of different species of flies. It bridges the gap between high-resolution, and high-throughput image processing methods, enabling us to quantify graded expression patterns along the antero-posterior axis of the embryo in an efficient and straightforward manner. Our method is based on a robust enzymatic (colorimetric) in situ hybridisation protocol and rapid data acquisition through wide-field microscopy. Data processing consists of image segmentation, profile extraction, and determination of expression domain boundary positions using a spline approximation. It results in sets of measured boundaries sorted by gene and developmental time point, which are analysed in terms of expression variability or spatio-temporal dynamics. Our method yields integrated time series of spatial gene expression, which can be used to reverse-engineer developmental gene regulatory networks across species. It is easily adaptable to other processes and species, enabling the in silico reconstitution of gene regulatory networks in a wide range of developmental contexts.

Understanding the complex regulatory networks underlying development and evolution of multi-cellular organisms is a major problem in biology. Computational models can be used as tools to extract the regulatory structure and dynamics of such networks from gene expression data. This approach is called reverse engineering. It has been successfully applied to many gene networks in various biological systems. However, to reconstitute the structure and non-linear dynamics of a developmental gene network in its spatial context remains a considerable challenge. Here, we address this challenge using a case study: the gap gene network involved in segment determination during early development of Drosophila melanogaster. A major problem for reverse-engineering pattern-forming networks is the significant amount of time and effort required to acquire and quantify spatial gene expression data. We have developed a simplified data processing pipeline that considerably increases the throughput of the method, but results in data of reduced accuracy compared to those previously used for gap gene network inference. We demonstrate that we can infer the correct network structure using our reduced data set, and investigate minimal data requirements for successful reverse engineering. Our results show that timing and position of expression domain boundaries are the crucial features for determining regulatory network structure from data, while it is less important to precisely measure expression levels. Based on this, we define minimal data requirements for gap gene network inference. Our results demonstrate the feasibility of reverse-engineering with much reduced experimental effort. This enables more widespread use of the method in different developmental contexts and organisms. Such systematic application of data-driven models to real-world networks has enormous potential. Only the quantitative investigation of a large number of developmental gene regulatory networks will allow us to discover whether there are rules or regularities governing development and evolution of complex multi-cellular organisms.

Background: Recurrent malignant pleural eff usion (MPE) is a common complication of breast carcinoma causing an irritating cough and pain due to the fl uid exerting pressure on the lungs. As the systemic therapy fails in approximately half of the patients with pleural eff usion, one of the palliative methods is used. Lately, the most commonly used procedure is the chemical pleurodesis with talc or the thoracoscopic mechanical pleurodesis. Th e aim of the study was to prove certain advantages of the latter method, especially at lower MPE pH values, since the chemical pleurodesis in those cases does not provide acceptable results. Methods: Th is prospective, randomized study included 87 patients with breast carcinoma and morphologically proven malignant pleural eff usion. Patients were divided into two groups according to palliative treatment: the TMP group (thoracoscopic mechanical pleurodesis) and the TP group (talc pleurodesis). Th ere were also four subcategories according to the pH value of malignant pleural eff usion (≥ 7.3, < 7.3). Results: Th e eff ectiveness (no recurrence of pleural eff usion) of TP (91 %) and TMP (92 %) was identical in patients with a MPE pH value above 7.3. However, in patients with pH value under 7.3 TMP was more successful (81 %) than TP (55 %). Th e lowest pH values at which the methods proved successful were 7.06 in TMP and 7.25 in TP. Conclusion: TP proved to be a more useful palliative method in patients with pH values above 7.3 due to its simplicity. On the other hand, TMP is more successful at lower pH values. Furthermore, TMP is also very eff ective in the group of patients with higher pH values, especially for handling cytologically or histologically unconfi rmed malignant pleural eff usions and in suspected adhesions in the pleural space.

Gene regulatory networks are perhaps the most important organizational level in the cell where signals from the cell state and the outside environment are integrated in terms of activation and inhibition of genes. For the last decade, the study of such networks has been fueled by large-scale experiments and renewed attention from the theoretical field. Different models have been proposed to, for instance, investigate expression dynamics, explain the network topology we observe in bacteria and yeast, and for the analysis of evolvability and robustness of such networks. Yet how these gene regulatory networks evolve and become evolvable remains an open question. An individual-oriented evolutionary model is used to shed light on this matter. Each individual has a genome from which its gene regulatory network is derived. Mutations, such as gene duplications and deletions, alter the genome, while the resulting network determines the gene expression pattern and hence fitness. With this protocol we let a population of individuals evolve under Darwinian selection in an environment that changes through time. Our work demonstrates that long-term evolution of complex gene regulatory networks in a changing environment can lead to a striking increase in the efficiency of generating beneficial mutations. We show that the population evolves towards genotype-phenotype mappings that allow for an orchestrated network-wide change in the gene expression pattern, requiring only a few specific gene indels. The genes involved are hubs of the networks, or directly influencing the hubs. Moreover, throughout the evolutionary trajectory the networks maintain their mutational robustness. In other words, evolution in an alternating environment leads to a network that is sensitive to a small class of beneficial mutations, while the majority of mutations remain neutral: an example of evolution of evolvability.

Abstract: With the development of science and technology, cardiac pace maker implantation has become most frequently performed operative procedure on the heart. The initial surgically rather complicated transthoracic approach and epicardial electrode cathether insertion was followed by the technically much easier transvenous approach and cathether insertion at the optimal site of the endocardium. In recent years, video-assisted thoracic surgery has established its undisputed place in epicardial electrode cathether insertion. Due to its lower morbidity, it replaced the much more aggressive thoracotomy and sternotomy. Preoperative patient preparation improved, the multidisciplinary approach to pathology solution prevailed and consequently the number of complications decreased. Presented are some of the most frequent and – despite the improved operative technique – unavoidable surgical complications, as well as the surgical complications occuring in cardiac pace maker insertions performed at the Maribor Teaching Hospital Department of Thoracic Surgery during the 5-year period of 2000–2004.

Background. Major thoracic trauma is consistent with high mortality rate because of associated injuries of vital thoracic organs and dangerous complications. The flail chest occurs after disruption of the skeletal continuity of chest wall and demands because of its pathophysiological complexity rapid and accurate diagnosis and treatment.Conclusions. Basic pathophysiological mechanism of the flail chest is respiratory distress, which is provoked by pulmonary contusions and paradoxical chest wall motion. The treatment should be pointed to improvement and support of respiratory functions and include aggressive pain control, pulmonary physiotherapy and selective mechanical ventilation. Views about operative fixation of the flail chest are still controversial. Neither mortality rate neither long-term disability are improved after operative fixation.

Purpose: Obesity, insulin resistance (IR), and proinflammatory cytokines associate with cognitive decline. Numerous studies document cognitive benefits of acute exercise bouts in lean individuals. However, how co-morbidities such as obesity and IR influence cognitive changes induced by acute exercise is unclear. We examined the effects of acute high-intensity aerobic exercise on cognitive function in age-matched and BMI-matched obese adults with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT) and in lean, NGT adults., Methods: 49 adults (15 Lean, 18 Obese-NGT, 16 Obese-IGT) performed one session of high-intensity interval exercise (four cycles of 4-min at 75% W max with 3-min rest). Cognitive function testing and blood sampling were performed pre- and post-exercise., Results: Following exercise, measurements of executive function and working memory were improved in Lean and Obese-NGT (p < 0.05), but not Obese-IGT. Changes in cognitive function following exercise negatively correlated with 2-hr glucose during an OGTT after controlling for body weight and body composition (r p  = -0.40, p = 0.007). Serum levels of inflammatory cytokines IL-6 and CRP remained increased 60-minutes post-exercise in Obese-IGT, but not in Lean or Obese-NGT, which positively associated with 2-hr glucose during an OGTT (p < 0.01) and negatively with changes in cognitive function following exercise (p < 0.01). Greater insulin levels in Obese-IGT post-exercise also negatively correlated with changes in cognitive function following exercise (p < 0.01)., Conclusion: Improvements in cognition following acute high-intensity exercise positively associate with glucose tolerance, independent of body weight and body composition. Further, poorer changes in cognitive performance following exercise associate with persistent peripheral inflammation., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Decreasing facial contact takes on new urgency as society tries to stem the tide of COVID-19 spread. A better understanding of the pervasiveness of facial contact in social settings is required in order to then take steps to mitigate the action., Methods: YouTube videos of random individuals were included in a behavioral observation study to document rates of contact to the eyes, nose, and mouth area. Factors including age, sex, the presence of eyewear or facial hair, distraction and fatigue were analyzed as possible contributing factors that increase likelihood of facial contact., Results: The median rate of facial contact was 22 contacts per hour. Men had a significantly higher rate of facial contact compared to women. Age, glasses, and presence of facial hair were not contributing factors. The mouth was the most frequently observed site of contact. Fatigue and distraction may increase rates of facial contact., Conclusions: Changing personal behavior is a simple and cost-effective action that can be employed to reduce one's risk of acquiring an infectious disease. This study indicates that there are societal differences that put some individuals at higher risk of contracting infectious disease than others., (Copyright © 2020 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Unusual or prominent calcifications found on screening mammography may prompt additional radiologic and clinical work-up given the possible association with pre-malignant lesions, other high-risk lesions, or malignancies. Osseous metaplasia (OM) of the breast, also referred to as metaplastic ossification or heterotopic bone formation, is an uncommon finding that may present as radiographic calcification. There are isolated case reports of OM associated with benign or malignant tumors of the breast, as well as with a variety of non-neoplastic conditions. We report 2 cases of OM in the breast associated with a hemangioma and review the relevant literature. To the best of our knowledge, these are the first reported cases of this association in the breast., Competing Interests: The authors declare that they have no competing interests., (© 2021 Korean Breast Cancer Society.)

Unlabelled: There is no doubt that the association between infection of the cervical epithelium by carcinogenic Human Papilloma Virus (HPV), particularly types 16 and 18, and cervical cancer (CC) is responsible for the activation of the immune response (IR). Research on tumor infiltrating lymphocytes at the primary tumor site could give us important information on how the immune cells are fighting against cancer., Aim: The aims of our study were to assess HPV status and to evaluate the significance of in situ cellular IR in CC., Materials and Methods: We performed a two-step retrospective analysis of IR in 18 CC: evaluation of HPV 16 and 18 infections by in situ hybridization and immune biomarkers (CD20, CD3, CD45) by immunohistochemistry. Immune cell profile, densities (assigned scores "0" if no inflammatory infiltrate, "1+" low, "2+" intense), tissue distribution and classical negative prognosis factors in relationship with survival and relapse were further assessed., Results: We successfully demonstrated HPV 16 and/or 18 in all cases. We reported statistical significant correlations (p<0.005) between CD3, CD20, CD45 and survival (r=0.800), relapse (r=-0.892), clinical stage (r=-0.914), tumor size (r=-1) as well as the association between survival and CC subtype (r=0.548), FIGO stage (r=-0.914), tumor size (r=-0.800) and grading (r=0.61)., Conclusions: The density of different immune cells is significantly involved in guiding prognosis of the CC in high-risk 16 and 18 HPV positive women; low cellular densities for CD3, CD20 and CD45 meaning limited immune response reflect negative disease outcomes promoting local relapse and decreased survival in such settings.

Unlabelled: Thrombotic thrombocytopenic purpura (TTP) is a rare but severe disease characterized by mechanical hemolytic anemia and consumptive thrombocytopenia leading to disseminated microvascular thrombosis that causes signs and symptoms of organ ischemia and functional damage. TTP is diagnosed by the presence of microangiopathic hemolytic anemia and thrombocytopenia in a patient who frequently presents with central nervous system involvement and, to a lesser extent, renal dysfunction., Case Report: We present the case of a 23-year-old female with TTP, diagnosed by the presence of the neurological symptoms, microangiopathic hemolytic anemia and severe thrombocytopenia (platelets 4000/μL). During the clinical evolution, the patient presented the hepatic cytolysis syndrome, following disseminated microvascular thrombosis inside the liver, representing an atypical damage. The diagnosis was difficult because it was necessary to make differential diagnosis with other diseases that evolve with microangiopathic hemolytic anemia in a short time to be able to initiate plasmapheresis. Initiation of the plasmapheresis as soon as possible was the goal of our treatment. Following the plasmapheresis combined with administration of corticosteroids was achieved complete resolution of all symptoms., Conclusions: TTP is a hematological emergency and diagnostic challenge. The critical determinant of outcome is timely diagnosis and treatment. Once the diagnosis is suspected, life-saving therapeutic plasma exchange therapy is initiated.

Unlabelled: Rheumatoid myositis (RM) is still poorly characterized, albeit the concept of muscle involvement in rheumatoid arthritis (RA) is well-recognized as being driven by a wide range of causes including inflammation, drugs, impaired joint flexibility, sedentarism., Objective: To describe clinical, serological, imaging and histological pattern of RM., Materials and Methods: This is a retrospective study on eight RM selected from a cohort of one hundred and three RA systematically assessed for skeletal muscle involvement. Data collected included clinical, serum muscle enzymes, muscle imaging and biopsy (Hematoxylin-Eosin, modified Gömöri trichrome staining)., Results: Routine muscle histology indicated both non-specific muscle fiber damage (changes in fiber size and internal structure: pleomorphic mitochondria, dilated sarcotubular system, multiple internal or subsarcommal nuclei; abnormal fiber types distribution: trend towards type II; atrophy; degenerative/regenerative modifications) and the presence of inflammatory deposits in all patients (mild to moderate, patchy B- and T-cells infiltrates, mainly perivascular and endomysial, but also in the perimysial region classified as polymyositis-like deposits). High levels of serum muscle enzymes, abnormal EMG (short duration, small amplitude, polyphasic motor unit action potentials) without insertional activity and fibrillations, active inflammation on both Doppler ultrasound and MRI were commonly reported., Conclusions: Traditional analysis of muscle biopsy specimens (Hematoxylin-Eosin, modified Gömöri trichrome staining) is faraway unsatisfactory, only documenting changes in muscle fibers size, architecture, internal structure, and, possibly, detecting perivascular, perimysial or endomysial inflammatory deposits. Upcoming research should address the value of muscle imaging for the diagnosis and evaluation of treatment response and muscle function in rheumatoid myositis.

Gastrointestinal stromal tumors (GISTs) are currently defined as c-Kit-positive mesenchymal tumors with specific histological characteristics. CD117 (c-Kit protein) is a growth factor receptor with tyrosine kinase activity and product of the protooncogene c-Kit. The most frequent sign is gastrointestinal haemorrhage, which occurs in approximately one third of patients. The evaluations which are necessary for diagnosis include clinical examination, immunohistochemistry analysis, endoscopic examination, X-ray, abdominal CT scan, ultrasound, MRI, exploratory surgery, biopsy or fine-needle aspiration of the tumor. Current data suggest a major role of a new tyrosine kinase inhibitor, imatinib mesylate (Glivec), for patients with metastatic or advanced disease. Surgical resection is the treatment of choice and offers the only chance for cure.

Diverticular disease of the colon, which is an acquired disorder caused by mucosal herniation through the colonic wall, has been termed both a "disease of the 20th century" and a "disease of Western civilization" due to its increasing prevalence in modern times and its striking geographical variability. There are complex relations between colonic structure, motility, and dietary factors, and it is likely that all of these play a role in the pathogenesis to a greater or lesser degree. Although present in two thirds of the elderly population, the large majority of patients will remain entirely asymptomatic. Nonetheless, 20% of those affected may manifest clinical illness and complications. Barium exploration indicates the extent and severity of colonic diverticular disease. Colonoscopy is preferred in positive diagnosis of uncomplicated diverticulosis. Computed tomography is especially useful in complicated diverticular disease. The use of high fibre diets in the prevention and treatment of the symptoms of diverticular disease has now become commonplace. The morbidity and mortality associated with complications, demand that this condition should receive greater attention in terms of aetiology, prevention and management.

Gastroesophageal reflux disease (GERD) symptoms are common in pregnancy, occurring in approximately 45% to 80% of pregnant women. Although the symptoms associated with reflux in pregnancy are similar to those described in the nonpregnant state, some of the etiologies are distinct due to hormonal fluctuations and other physiologic changes often associated with pregnancy. Diagnostic tools and therapeutic regimens that might be used without hesitation in the nonpregnant patient must be given with cautious consideration in the gravid patient due to potential fetal risks. Pregnant patients with symptomatic GERD should be managed aggressively with lifestyle modification and dietary changes. Antacids and antacids/alginic acids combination or sucralfate should be considered first-line medical therapy; treatment with cimetidine or ranitidine should be considered; these H2 receptor antagonists are preferred during pregnancy. Proton-pump inhibitors should be used with caution because little human experience is available.

About 2 per cent of the deliveries are recorded in patients with heart diseases. Between 1983 and 1987, 30 pregnant women with congenital cardiovascular diseases (CCVD) were studied retrospectively on the basis of clinical observation cards and operation records. Detected during the first trimester of pregnancy, 13 cases underwent therapeutical abortion, in a case in whom life was threatened a hysterotomy was performed while 16 CCVD cases carried on their pregnancies to the end. Eleven of them delivered by caesarean section and 5 had a natural delivery. In a patient with dissecting aneurysm of aorta (Marfan's syndrome) death occurred after caesarean section. Six CCVD had been corrected by previous surgery. In conclusion it is stated that in pregnant women CCVD is a high risk. Surgical correction of CCVD, preferably outside the pregnancy period, is the best prophylaxis of the incidents in the cardiac pregnant women.