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The aim was to compare the lipid profile of patients with GD treated with anti-thyroid drugs (ATDs) using a titration regimen versus a block and replace regimen. This is an 18-month prospective observational study. In this study were included 149 medically treated GD patients, aged+>+18 years. Pregnant women and patients treated with radioactive iodine therapy or partial/total thyroidectomy were excluded. Patients were divided into 2 subgroups: titration (A) and block and replace (B) therapy, according to the ATD regimen used. Thyroid and metabolic profile was measured at baseline and at least one visit during medical treatment. The whole group included 122 (81.87%) females (F) and 27 (18.12%) males (M), ratio F:M=4.5:1. As expected, at the time of diagnosis, thyrotoxic patients were with normal lipid profile. During medical treatment, in patients who achieved euthyroidism, the cholesterol levels increased as follows: in subgroup A: by 52.9 mg/dl (95% CI: 26.4-79.3), p<0.001 for total cholesterol (T-C), by 33.3 mg/dl (95% CI: 10.3-56.3), p=0.007 for low-density lipoprotein cholesterol (LDL-C) and by 11.44 mg/dl (95% CI: 3.08-19.79), p=0.009 for high-density lipoprotein cholesterol (HDL-C); in subgroup B T-C increased by 45.1 mg/dl (95% CI: 22.2-68), p<0.001 and for LDL-C by 33.57 mg/dl (95% CI: 12.72-54.42), p=0.003. No statistically significant increase in triglyceride levels was determined. Medical treatment of hyperthyroidism due to Graves' disease increased cholesterol levels regardless of the ATD regimen used., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Colorectal cancer (CRC) brain metastasis (BM) is a rare but aggressive manifestation of the disease, with poor prognosis and limited treatment options. Although brain metastases are more commonly associated with primary tumors located in the lung, skin, and breast, their occurrence in colorectal cancer is uncommon. Genetic mutations are highly important in tumor progression, and mutations in KRAS and BRAF genes are key drivers in colorectal cancer. However, the concurrent presence of both mutations is exceedingly rare. This case report presents a unique instance of colorectal cancer brain metastasis harboring both KRAS and BRAF mutations, highlighting its clinical significance and therapeutic challenges. We present the case of a 62-year-old male patient diagnosed with brain metastasis (in the cerebellum and right parietal lobe) who presented to the hospital with neurological symptoms. He underwent a CT imaging investigation that revealed multiple tumors. Subsequent biopsies confirmed the diagnosis of brain metastasis, with histological characteristics consistent with colonic adenocarcinoma. Tests also revealed aberrant expression of both KRAS and BRAF mutations. This case highlights the importance of considering brain metastases in colorectal cancer patients due to their detrimental effects on prognosis and survival rates. Additionally, the simultaneous presence of BRAF and KRAS mutations, in this case, adds an extra layer of complexity and severity., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Comisia de Etica a Cercetarii - FMF Oradea issued approval N/A. The Comisia de Etica a Cercetarii, at FMF Oradea , has reviewed and approved the case report entitled "Colorectal Cancer Brain Metastasis with Concomitant KRAS and BRAF Mutations: A Case Report." The committee has determined that the study adheres to the ethical standards required for clinical research, including respect for patient confidentiality, informed consent, and the responsible use of clinical data . Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Vesa et al.)

In the actual context of growing concerns over sustainability and energy efficiency, Phase Change Materials (PCMs) have gained attention as promising solutions for enhancing energy storage and release efficiency. On another hand, materials based on graphene oxide (GO) have proven antibacterial activity, biocompatibility, efficiency in microbial growth inhibition, and pollutant removal. Integrating nanoparticles into PCMs and creating Nano-Enhanced Phase Change Materials (NEPCMs) have opened new horizons for optimizing the performance of these systems and sustainable development. The key objective of this work is to gain insight into NECPMs, which are used in solar wall systems to enhance solar energy storage. Paraffin RT31 was mixed with Cu nanoparticles, graphene oxide (GO), and Cu-decorated GO (Cu@GO) at loading ratios ranging from 1% to 4% ( w / w nanoparticles with respect to RT31). The compositions were characterized through Differential Scanning Calorimetry (DSC) and rheology tests. The decoration of the carbon-based nanoparticles was performed using the ultrasonication procedure, and the decoration efficiency was confirmed through X-ray Photoelectron Spectroscopy (XPS). The rheologic measurements were performed to correlate the flow behavior of the NEPCM with their composition at various temperatures. The study methodically investigated these composites' latent heat values, phase change peak temperatures, and solidification phase change temperatures. Compared to pure paraffin, the solidification of the formulations obtained using Cu@GO exhibits the largest increase in latent heat, with a 12.07% growth at a concentration of 2%. Additionally, at a 4% concentration of NEPCM, the largest increase in thermal conductivity was attained, namely 12.5%.

The effect of microfluidization treatment on the primary, secondary, and tertiary structure of soybean protein isolate (SPI) was investigated. The samples were treated with and without controlling the temperature and circulated in the system 1, 3, and 5 times at high pressure (137 MPa). Then, the treated samples were freeze-dried and reconstituted in water to check the impact of the microfluidization on two different states: powder and solution. Regarding the primary structure, the SDS-PAGE analysis under reducing conditions showed that the protein bands remained unchanged when exposed to microfluidization treatment. When the temperature was controlled for the samples in their powder state, a significant decrease in the quantities of β-sheet and random coil and a slight reduction in α-helix content was noticed. The observed decrease in β-sheet and the increase in β-turns in treated samples indicated that microfluidization may lead to protein unfolding, opening the hydrophobic regions. Additionally, a lower amount of α-helix suggests a higher protein flexibility. After reconstitution in water, a significant difference was observed only in α-helix, β-sheet and β-turn. Related to the tertiary structure, microfluidization increases the surface hydrophobicity. Among all the conditions tested, the samples where the temperature is controlled seem the most suitable., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: This research explored how crises such as the pandemic influence the family dynamic and the way that the parents and the children face new difficulties and challenges. The present study investigates children's and young people's emotional states, the dimensions of family resilience, and the types of coping strategies and parents' emotional states during the coronavirus pandemic. The final sample for the research was represented by 1,010 parents from Romania., Methods: The present scientific research is a transversal study with the scope to understand the emotional difficulties that parents and children/ young people face and the coping strategies that they adopt in a crisis, such as the time of the coronavirus pandemic., Results: Parents with maladaptive coping strategies are more affected by the pandemic. Also, the results indicate that there is a significant correlation between parental coping strategies and the children's emotional states, and the adaptability level. Therefore, the high scores on the subscales which measure maladaptive coping indicate high scores of the levels of depression, anxiety, and stress of the parents. Family resilience, through the dimension of 'communication and problem-solving in the family' has a moderation role in the relationship between parental depression and the maladaptive coping strategy of rumination. Family resilience through 'maintaining a positive attitude' has a moderation role in the relationship between catastrophizing and the teenagers' level of adaptability., Discussion: The results of the study pointed out the role and place of family resilience within the family system and how a period of crisis can affect this system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Vladislav, Marc, Paica and Pop.)

Background: The increasing incidence of colorectal cancer is one of the most frequently addressed medical topics worldwide. It represents the third most commonly diagnosed cancer in both men and women globally, with significant implications for public health. Mortality for this type of malignancy remains high, second only to lung cancer. Given their clinical relevance, the identification and understanding of KRAS and BRAF mutations have become crucial components of personalized medicine approaches in colorectal cancer. Hence, our desire is to carry out a research that analyzes the impact of these mutations in terms of survival and mortality on patients diagnosed with colorectal cancer., Methods: We conducted a retrospective study spanning from 2018 to 2022, which involved 118 patients diagnosed with colorectal cancer. The patients were selected from the databases of the Oradea County Emergency Clinical Hospital and Pelican Oradea Hospital. Genetic testing was performed at the "Resident Laboratory" clinic. Subsequently, patients were divided into two groups of equal size based on the presence or absence of mutations., Results: The survival rate one year after the diagnosis of colorectal cancer is 84.74% (N=50/59) for the mutant group versus 67.96% (N=40/59) for the wild-type group. The survival rate at five years from the diagnosis of colorectal cancer is 25.93% (N=15/59) for patients with wild-type tumors compared to 33.54% (N=20/59) for patients with tumors with mutant status (p=0.483, HR=1.153, CI 95% 0.7661-1.735). The five-year survival rate, depending on the mutation present, highlights the fact that the average overall survival for those with the KRAS mutation is 38.6 months (CI 95% 35.22-41.97) and for those with the BRAF mutation is 8.3 months (CI 95% 5.42-11.17) (p=0.039). The mortality rate for mutant KRAS is 44.89% (N=22/50), while for those with mutant BRAF, it is 100% (N=6/6)., Conclusions: We observed no statistically significant difference in overall survival rate and disease-free interval between the two studied groups, but the overall survival was better for those with mutations present (38.64 months versus 31.07 months for wild-type tumors). The mortality rate is higher among tumors with wild-type status (p=0.005), in the first year after the diagnosis of colorectal cancer. The BRAF mutation confers a much worse prognosis than the KRAS mutation, from both the survival analysis and the mortality rate., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Vesa et al.)

Background: Estimating the excess of premature deaths (before the age of 75 years) and Potential Years of Life Lost allows ranking causes of death as an expression of the burden of disease in a population. We statistically analysed the impact of the coronavirus disease 2019 (COVID-19) pandemic on excess premature mortality in the total population and specifically, by sexes, compared to the pre-pandemic period, through Potential Years of Life Lost., Material and Method: In this retrospective descriptive observational study, we counted excess of premature mortality in the years 2020, 2021, and 2022 by cause of death (cardiovascular diseases, cancer, digestive diseases, injury, COVID-19, and other causes) and by sexes compared to the period average from 2017-2019, based on the deaths registered in Bihor County (48,948 people)., Results: Premature deaths due to COVID-19 (1,745 people of both sexes) contributed 71.3% to excess mortality, the population being similar for both sexes (71.4% in men and 71.2% in women). The Potential Years of Life Lost/death due to COVID-19 was 11.84 years for both sexes (11.76 years in men and 12.02 years in women). Potential Years of Life Lost/all-cause heath was lower during the pandemic (13.42 years for both sexes, 14.06 years for men and 12.32 years for women) compared to the pre-pandemic period (14.6 years for both sexes, 15.1 years for men and 13.5 years for women)., Conclusions: The excess of premature mortality and decreased Potential Years of Life Lost/death during the pandemic, shows an increase in the proportion of deaths at ages closer to the established limit for premature mortality (75 years) compared to the pre-pandemic period., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Rahota et al.)

Background/aim: H. pylori infection can promote a systemic inflammatory syndrome, eventually leading to intestinal metaplasia and gastric cancer. The aim of our study was to investigate the possible association between dyslipidemia and histopathological features of H. pylori gastritis., Patients and Methods: An observational, retrospective study was conducted over the period 2017-2022 on symptomatic patients with a positive rapid urease test. A total of 121 patients who underwent upper gastrointestinal endoscopy with stomach biopsy were enrolled in this study. Based on the updated Sydney System, we investigated the association between neutrophils, mononuclear cells, intestinal metaplasia, or gastric atrophy and altered lipid profiles., Results: A high prevalence of H. pylori infection was noticed in the studied group upon the application of the rapid urease test, being associated with dyslipidemia regardless of patient sex. All the endoscopic diagnoses (acute, chronic, or atrophic chronic gastritis, metaplasia) correlated with the histopathological features. Mononuclear cells and metaplasia were more likely to be found in H. pylori-positive patients with dyslipidemia, which is consistent with acute and chronic inflammation caused by H. pylori in the gastric mucosa., Conclusion: Although our study was conducted on a small scale, it offers new insights and details regarding H. pylori infection and histopathological features. Mononuclear cells and metaplasia were associated with an altered lipid profile in H. pylori-positive patients. These findings warrant future investigation, such as the evolution of gastric biopsies and lipid profiles before and after eradication., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The effect of optical radiation during the phase transition from the amorphous to the crystalline state of matter was investigated for the first time. The results were obtained on nanoscale films of (LiF) x (Li 2 B 4 O 7 ) 1-x compositions by sputtering on cold Ni substrates. The starting materials for films were chosen due to their wide use for tissue-equivalent ionizing radiation dosimetry. It is shown that the detected thermoluminescence effect is sensitive to the thickness of the films. The paper compares the results of these studies with the study of the thermoluminescence characteristics of films irradiated by an M-30 microtron with bremsstrahlung radiation with a maximum energy of 6 MeV. The absorbed radiation dose was 1 kGy. Differences in the luminescence characteristics of irradiated and nonirradiated films were revealed. The nature of the demonstrated structural-optical effect is discussed., (© 2024 John Wiley & Sons Ltd.)

Research indicates compelling evidence of SARS-CoV-2 vertical transmission as a result of placental pathology. This study offers an approach to histopathological and immunohistochemical placental observations from SARS-CoV-2-positive mothers compared to negative ones. Out of the 44 examined placentas, 24 were collected from patients with a SARS-CoV-2 infection during pregnancy and 20 were collected from patients without infection. The disease group showed strong SARS-CoV-2 positivity of the membranes, trophoblasts, and fetal villous macrophages. Most infections occurred during the third trimester of pregnancy (66.6%). Pathology revealed areas consistent with avascular villi (AV) and thrombi in the chorionic vessels and umbilical cord in the positive group, suggesting fetal vascular malperfusion (FVM). This study shows SARS-CoV-2 has an impact on coagulation, demonstrated by fetal thrombotic vasculopathy ( p = 0.01) and fibrin deposition ( p = 0.01). Other observed features included infarction (17%), perivillous fibrin deposition (29%), intervillous fibrin (25%), delayed placental maturation (8.3%), chorangiosis (13%), chorioamnionitis (8.3%), and meconium (21%). The negative control group revealed only one case of placental infarction (5%), intervillous fibrin (5%), delayed placental maturation (5%), and chorioamnionitis (5%) and two cases of meconium (19%). Our study sheds light on the changes and differences that occurred in placentas from SARS-CoV-2-infected mothers and the control group. Further research is necessary to definitively establish whether SARS-CoV-2 is the primary culprit behind these intricate complications.

The application of artificial intelligence to improve the access of cancer patients to high-quality medical care is one of the goals of modern medicine. Pathology constitutes the foundation of modern oncologic treatment, and its role has expanded far beyond diagnosis into predicting treatment response and overall survival. However, the funding of pathology is often an afterthought in resource-scarce medical systems. The increased digitalization of pathology has paved the way towards the potential use of artificial intelligence tools for improving pathologist efficiency and extracting more information from tissues. In this review, we provide an overview of the main research directions intersecting with artificial intelligence and pathology in relation to oncology, such as tumor classification, the prediction of molecular alterations, and biomarker quantification. We then discuss examples of tools that have matured into clinical products and gained regulatory approval for clinical use. Finally, we highlight the main hurdles that stand in the way of the digitalization of pathology and the application of artificial intelligence in pathology while also discussing possible solutions.

Olive leaf was characterized by a high content of phenols and flavonoids (oleuropein, luteolin, and their derivatives), presenting functional and health-related properties. The chemical instability of phenolics through technological processes and their degradation in the digestive system may negatively impact them, leading to lower absorption. This study evaluates the phenolic profile of micro- and nano-encapsulated olive leaf extract in biscuits during the INFOGEST static in vitro digestion, aiming to enhance stability and sensorial properties. Ultrasound-assisted extraction and chromatography characterized the extract, while spray drying (maltodextrin-glucose) and nano-encapsulation (maltodextrin, whey protein isolate, and arabic gum) techniques were used with specific solutions. Encapsulated formulations underwent microscopy (TEM, SEM) and encapsulation efficiency analysis. Micro- and nano-encapsulation improved biscuit functionality by enhancing phenolic stability during digestion. However, the highest concentration adversely affected sensory and textural parameters. These findings contribute to developing functional food products enriched with bioactive compounds, providing improved health benefits while maintaining sensory attributes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: The role of autoreactive T cells on the course of Coronavirus disease-19 (COVID-19) remains elusive. Type II pneumocytes represent the main target cells of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Autoimmune responses against antigens highly expressed in type II pneumocytes may influence the severity of COVID-19 disease., Objective: The aim of this study was to investigate autoreactive T cell responses against self-antigens highly expressed in type II pneumocytes in the blood of COVID-19 patients with severe and non-severe disease., Methods: We collected blood samples of COVID-19 patients with varying degrees of disease severity and of pre-pandemic controls. T cell stimulation assays with peptide pools of type II pneumocyte antigens were performed in two independent cohorts to analyze the autoimmune T cell responses in patients with non-severe and severe COVID-19 disease. Target cell lysis assays were performed with lung cancer cell lines to determine the extent of cell killing by type II PAA-specific T cells., Results: We identified autoreactive T cell responses against four recently described self-antigens highly expressed in type II pneumocytes, known as surfactant protein A, surfactant protein B, surfactant protein C and napsin A, in the blood of COVID-19 patients. These antigens were termed type II pneumocyte-associated antigens (type II PAAs). We found that patients with non-severe COVID-19 disease showed a significantly higher frequency of type II PAA-specific autoreactive T cells in the blood when compared to severely ill patients. The presence of high frequencies of type II PAA-specific T cells in the blood of non-severe COVID-19 patients was independent of their age. We also found that napsin A-specific T cells from convalescent COVID-19 patients could kill lung cancer cells, demonstrating the functional and cytotoxic role of these T cells., Conclusions: Our data suggest that autoreactive type II PAA-specific T cells have a protective role in SARS-CoV-2 infections and the presence of high frequencies of these autoreactive T cells indicates effective viral control in COVID-19 patients. Type II-PAA-specific T cells may therefore promote the killing of infected type II pneumocytes and viral clearance., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

According to the latest data provided by Globocan 2020, the incidence of colorectal cancer ranks third, after lung cancer and breast cancer, becoming a more and more important global health issue. Of the cases diagnosed with colorectal cancer, more than 25% are diagnosed in the metastatic stage, with the presence of secondary tumors more frequently in the liver, lung and bone. Skin metastases from colorectal cancer are still rare today (< 4%). We want to present a rare, unique case in our department of a 74-year-old patient diagnosed 9 years ago with a malignant rectal tumor who, after a disease-free period of approximately 8 years and a half, developed multiple skin metastases of rectal adenocarcinoma.

The primary objective of this investigation was to determine the hub genes of hepatocellular carcinoma (HCC) through an in silico approach. In the current context of the increased incidence of liver cancers, this approach could be a useful prognostic biomarker and HCC prevention target. This study aimed to examine hub genes for immune cell infiltration and their good prognostic characteristics for HCC research. Human genes selected from databases (Gene Cards and DisGeNET) were used to identify the HCC markers. Further, classification of the hub genes from communicating genes was performed using data derived from the targets' protein-protein interaction (PPI) platform. The expression as well as survival studies of all these selected genes were validated by utilizing databases such as GEPIA2, HPA, and immune cell infiltration. Based on the studies, five hub genes (TP53, ESR1, AKT1, CASP3, and JUN) were identified, which have been linked to HCC. They may be an important prognostic biomarker and preventative target of HCC. In silico analysis revealed that out of five hub genes, the TP53 and ESR1 hub genes potentially act as key targets for HCC prevention and treatment., (© 2022. The Author(s).)

Diabetes mellitus (DM) is a metabolic syndrome. Diabetes has become more common in recent years. Chemically generated drugs are used to lessen the effects of DM and its following repercussions due to unpleasant side effects such as weight gain, gastrointestinal issues, and heart failure. On the other hand, medicinal plants could be a good source of anti-diabetic medications. This article aims to determine any plant matrix's positive potential. Food restriction, physical activity, and the use of antidiabetic plant-derived chemicals are all being promoted as effective ways to manage diabetes because they are less expensive and have fewer or no side effects. This review focuses on antidiabetic plants, along with their bioactive constituent, chemically characterization, and plant-based diets for diabetes management. There is minimal scientific data about the mechanism of action of the plant-based product has been found. The purpose of this article is to highlight anti-diabetic plants and plant-derived bioactive compounds that have anti-diabetic properties. It also provides researchers with data that may be used to build future strategies, such as identifying promising bioactive molecules to make diabetes management easier., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The paper proposed an alternative optical metrology to classical methods (strain gauge measurements and numerical simulation) for strain determination on printed circuit board (PCBs) due to thermal loads. The digital image correlation (DIC) technique was employed to record the strain distribution in some particular areas of the PCB. A thermal load was applied using a heating chamber, and the measurements were performed at four different temperature steps (25 °C, 50 °C, 85 °C and 120 °C). An increase in the principal strains with temperature was observed. For validation, the principal strains on the PCB obtained with DIC were compared with the values from gauge strain measurements and numerical simulation. The conclusions highlighted that DIC represents a technique with potential for strain measurement caused by thermal deformation, with the advantages of full field measurement, less preparation of the surface and good accuracy.

Sepsis-induced myocardial dysfunction (SIMD) is one of the major predictors of morbidity and mortality of sepsis. A high percentage of patients with SIMD develop a status similar to cardiogenic shock. A high level of bacterial lipopolysaccharide (LPS) associated with an overexpression of CD14 acts as the trigger for the release of a broad spectrum of cytokines. Our study aimed to understand the correlation between septic cardiomyopathy and CD14 immunohistochemical expression. The study included 29 patients who died of septic shock. Increased values of membranous CD14 and soluble CD14 in the heart tissue were correlated with adverse patient evolution. A high cellular expression of CD14 was noted in the study group vs. the control group ( p = 0.0013). Therefore, a close positive association between the amount of LPS related to sCD14 and the cellular expression of mCD14 is probable. By extrapolation, we suggest that a large amount of sCD14 detected in the cardiac tissue will activate the mCD14-TRL4-LBP-LPS complex, which in turn will induce an inadequate immune response, resulting in heart damage proportional to the amount of LPS. CD14 could represent a valuable marker for septic cardiomyopathy; thus, apoptosis of cardiomyocytes could be foreseen by its high value.

Rapid diagnosis and treatment application in the early stages of H. pylori infection plays an important part in inhibiting the transmission of this infection as this bacterium is involved in various gastric pathologies such as gastritis, gastro-duodenal ulcer, and even gastric neoplasia. This review is devoted to a quick overview of conventional and advanced detection techniques successfully applied to the detection of H. pylori in the context of a compelling need to upgrade the standards of the diagnostic methods which are currently being used. Selecting the best diagnostic method implies evaluating different features, the use of one or another test depending on accessibility, laboratories equipment, and the clinical conditions of patients. This paper aims to expose the diagnosis methods for H. pylori that are currently available, highlighting their assets and limitations. The perspectives and the advantages of nanotechnology along with the concept of nano(bio)sensors and the development of lab-on-chip devices as advanced tools for H. pylori detection, differentiation, and discrimination is also presented, by emphasizing multiple advantages: simple, fast, cost-effective, portable, miniaturized, small volume of samples required, highly sensitive, and selective. It is generally accepted that the development of intelligent sensors will completely revolutionize the acquisition procedure and medical decision in the framework of smart healthcare monitoring systems.

Objective: To evaluate the efficacy and safety of regorafenib versus tamoxifen in platinum-sensitive ovarian cancer biological recurrence, defined by CA-125 increase without radiological (RECIST criteria) or symptomatic evidence of progression., Patients and Methods: 116 patients with platinum-sensitive ovarian cancer presenting an isolated increase of CA-125 were planned to be randomized. Regorafenib was administered orally at 160 or 120 mg daily, 3 weeks on/1 week off or tamoxifen at 40 mg daily, until disease progression or development of unacceptable toxicity. The primary endpoint was Progression-Free Survival, assessed by progression according to RECIST 1.1 or death (by any cause). Secondary endpoints included Overall Survival, Best Response and CA-125 response rate., Results: 68 patients were randomized. Median age was 67 years (range: 30-87). Primary site of cancer was ovarian for most patients (92.6%). Tumors were predominantly serous / (89.7%), high grade (83.6%) and initial FIGO staging was III for 69.6% of the patients. Most (79.4%) patients were included after the first line of platinum-based treatment. After a median follow-up of 32 months, there was no difference of progression-free survival (PFS) between regorafenib and tamoxifen groups (p = 0.72), with median PFS of 5.6 months (CI 90%: 3.84-7.52) for the tamoxifen arm and 4.6 months (CI 90%: 3.65-7.33) for the regorafenib arm. There was also no difference in term of overall survival, best response or CA-125 response, delay to next therapy. Regorafenib presented a less favorable safety profile than tamoxifen, with grade 3/4 events occurring for 90.9% of the patients compared to 54.3% for tamoxifen. The most frequent were cutaneous, digestive, and biological events. Notably, hand-foot syndrome occurred in 36.4% of these patients., Conclusion: Regorafenib presented an unfavorable toxicity profile compared to tamoxifen, with no superior efficacy in this population of patients., Competing Interests: Declaration of Competing Interest Dr. Trédan reports supports from the present manuscripts to ARCAGY GINECO from Bayer HealthCare, grants or contracts from Roche, BMS and MSD-Merck (payments to his institution), consulting fees from Roche, Pfizer, Astra-Zeneca, Lilly, Novartis-Sandoz, Daiichi-Sankyo, Seagen Pierre Fabre, MSD-Merck, Eisai (payments to him), payments/honoraria from Roche, Pfizer, Astra-Zeneca, Lilly, Novartis-Sandoz, Daiichi-Sankyo, Seagen, Pierre Fabre, MSD-Merck, Eisai, support for attending meeting and/or travel from Roche, Astra-Zeneca, Pfizer (payments to him). Dr. Hardy-Bessard reports payment/honoraria from MSD, Astra-Zeneca, GSK and participation on data safety monitoring board/advisory board with Clovis, MSD, Astra-Zeneca, GSK, Novartis, Pfizer. Dr. Lortholary reports payment/honoraria from Astra-Zeneca, Roche, MSD, Clovis, Novartis, support for attending meetings/travel from Roche and Astra-Zeneca and participation in a Data Safety Monitoring Board/Advisory board with Astra-Zeneca, Roche, MSD, Clovis and Novartis. Dr. Frenel reports payments/honoraria from Astra Zeneca, Lilly, Daiichi, Pfizer, Amgen, support for attending meetings/travel from Pfizer and Astra Zeneca, and participation on a Data Safety Monitoring Board/advisory board from Pfizer, Lilly, Novartis, GSK, Astra-Zeneca, MSD, Roche and Clovis. Dr. Louvet reports payments/honoraria from Merck, Roche, Servier and Amgen and support for attending meetings/travels from Roche and Merck. Dr. You reports consulting fees from MSD, Astra-Zeneca, GSK, Bayer, Roche, ECS Progastrine, Novartis, LEK, Amgen, Clovis, Merck Serono, BMS, Seagen. Amélie Anota reports consulting fees from Roche, Astra-Zeneca, Sandoz, Pfizer/Hospira, payment or honoraria for lectures from Astra-Zeneca and BMS and support for attending meetings/travels from Roche, Astra-Zeneca and Novartis. Pr Ray-Coquard reports consulting fees from Amgen, Astra-Zeneca, Clovis Oncology, Genmab, GSK, ImmunoGen, Merck Sharp & Dohme, Pfizer/Merck-Sereno, PharmaMar, and Roche, grants/contracts with Roche, BMS, MSD, GSK Company and support for attending meetings/travels from Astra-Zeneca, Roche, GSK and Clovis. The remaining authors declare no conflict of interest., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a commonly used minimally invasive method for the diagnosis and staging of lung cancer. In order to improve its diagnostic accuracy, rapid on-site cytologic evaluation (ROSE) is being utilized in some institutions. ROSE, performed by a cytopathologist in the examination room, allows the assessment of the adequacy of the collected samples, identifies malignant cells and sometimes establishes diagnosis on the spot, thus improving diagnostic sensitivity. As non-small cell lung carcinomas (NSCLC) require not only pathological subtyping, but also molecular characterization, obtaining the adequate amount of tissue is crucial. Only a limited number of studies have analyzed the suitability of EBUS-TBNA samples for assessment of epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) and programmed death-ligand 1 (PD-L1) status., Aim: We intended to examine the diagnostic yield of ROSE in NSCLC and the results and feasibility of molecular analysis performed on EBUS-TBNA small samples., Methods: 100 patients with lung tumors and hilar and/or mediastinal lymphadenopathy on CT or PET/CT scans were retrospectively identified over a 3-year period, from a prospectively maintained EBUS-TBNA database. All examinations were accompanied by on-site cytological exam - ROSE, histopathological exam (HPE) and, in the case of NSCLC, molecular testing. After the sampling of the lymph nodes, specimens were Diff-Quik stained and a rapid preliminary diagnosis was established. Immunohistochemistry and mutational testing were performed using cell blocks., Results: Adenocarcinoma was the most frequent diagnosis in both ROSE (34%) and histopathology (53%). Overall sensitivity and positive predictive value of ROSE in NSCLC, considering HPE the gold standard, were 92.18% and 93.65%, respectively, with a specificity and negative predictive value of 75% and 70.58%, respectively. All samples that were tested for EGFR mutation and ALK rearrangement were adequate for analysis. The adequacy ratio for PD-L1 was 91.66%; 37.5% of patients showed a high PD-L1 expression level, with a tumor proportion score TPS ≥50%., Conclusion: EBUS-TBNA is a valuable method for lung cancer diagnosis. ROSE proved to have a moderate prediction of the final diagnosis in NSCLC. Molecular analysis of EGFR, ALK and PD-L1 can be successfully accomplished on EBUS-TBNA small tissue samples.

The efficiency of amniotic membrane (AM) transplantation in different types of ocular surface disorders is due to its outstanding properties such as antifibrotic, antibacterial, anti-inflammatory and antiangiogenic, working as a versatile scaffold to promote corneal tissue epithelialization. A proper preparation, preservation and clinical application are crucial for the best outcomes in the treatment of different severe ocular disorders, taking into account its fragility. In this context, by combining high-sensitivity tools such as atomic force microscopy (AFM) and Fourier transform infrared (FTIR) spectroscopy with histological and immunohistochemical examination, we aimed to investigate the ultrastructural modifications of the amniotic membrane (AM) upon UV exposure and/or antibiotic treatment, with relevance for clinical applications in ocular surface surgery. From the morphological point of view, we noticed a loss of cuboidal cells in the basal membrane, accompanied by the splitting of collagen fibers upon UV and/or gentamicin treatment, while structural alteration of proteins was evidenced by the FTIR quantitative analysis of the secondary structure. A decrease in α-helix and β-sheet content, accompanied by increased content in less ordered structures (turns, random and side chains), was noticed after all the treatments. At the nano-scale, AFM details showed modifications of collagen fibrils in terms of their thickness and network compaction upon gentamicin and/or UV treatment. The enzymatic digestion assay demonstrated that UV exposure significantly reduces the degradation rate of the AM, while gentamicin treatment promotes an accelerated enzymatic digestion upon UV exposure. In order to highlight the clinical impact of the research, a clinical case is presented showing the relevance of amniotic membrane transplantation in pterygium surgery.

Background: This study evaluated the consequences in Europe of the COVID-19 outbreak on pathology laboratories orientated toward the diagnosis of thoracic diseases., Materials and Methods: A survey was sent to 71 pathology laboratories from 21 European countries. The questionnaire requested information concerning the organization of biosafety, the clinical and molecular pathology, the biobanking, the workload, the associated research into COVID-19, and the organization of education and training during the COVID-19 crisis, from 15 March to 31 May 2020, compared with the same period in 2019., Results: Questionnaires were returned from 53/71 (75%) laboratories from 18 European countries. The biosafety procedures were heterogeneous. The workload in clinical and molecular pathology decreased dramatically by 31% (range, 3%-55%) and 26% (range, 7%-62%), respectively. According to the professional category, between 28% and 41% of the staff members were not present in the laboratories but did teleworking. A total of 70% of the laboratories developed virtual meetings for the training of residents and junior pathologists. During the period of study, none of the staff members with confirmed COVID-19 became infected as a result of handling samples., Conclusions: The COVID-19 pandemic has had a strong impact on most of the European pathology laboratories included in this study. Urgent implementation of several changes to the organization of most of these laboratories, notably to better harmonize biosafety procedures, was noted at the onset of the pandemic and maintained in the event of a new wave of infection occurring in Europe., Competing Interests: Disclosure The authors have declared no conflicts of interest. Data sharing Anonymized participant-level data are available for investigators. Ethical approval The study complied with the law of January 1978 (78-17) relating to computing, data, and freedom known as ‘computing and freedoms’ and with rules 2016/679 of the European Parliament (of 25 May 2018) concerning the general data protection regulation (GDPR; MR004). The study was registered by the Nice University Hospital (R04-39) and filed on the Health Data Hub website (7 July 2020) (www.health-data-hub.fr/depot)., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The accurate localization of small tumors of the digestive tract is of paramount importance in surgical oncology because it dictates the limits of resection and the extent of lymph node dissection. In this view, we have designed and fabricated a highly efficient sensing laparoscopic instrument focused on precise non-invasive extralumenal intraoperative detection of small colorectal or gastric tumors. The equipment is fully adapted for laparoscopic surgery and consists of an inductive proximity sensor encapsulated into a watertight stainless-steel case that is connected to an electronic functional block dimensionally scaled-down by the desired form and size for optimal surgical manipulation. The sensor-case unit and the electronic block are coupled together using a modular system which allows disconnection of the latter and sterilization by autoclavation of the former, followed by swift plugging of the electronic block just before surgery in a sterile-controlled environment. The instrument works in tandem with a modified endoscopic hemostatic clip which is attached endoscopically, before surgery, in the mucosa proximal and distal to the tumor. By scanning the serosal side of the digestive organ during the laparoscopic surgical procedure, the detector senses the modified clip and thus pinpoints to the location of the tumor. Additional engineering of the standard endoscopic hemostatic clips by coating them with various combinations of metallic alloys of Cu and Zn was necessary to improve the detection range and sensitivity without compromising on their functionality. The clips were also covered with nanometric layers of Au to ensure their biocompatibility. The ex-vivo dry-lab experiments showed a satisfactory detection distance which was later confirmed in ex-vivo wet-lab experiments on animal organs and human surgical specimens., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Workplace violence (WPV) has been extensively studied in hospitals, yet little is known about WPV in outpatient physician clinics. These settings and work tasks may present different risk factors for WPV compared to hospitals, including the handling/exchange of cash, and being remotely located without security presence. We conducted a systematic literature review to describe what is currently known about WPV in outpatient physician clinics. Six literature databases were searched and reference lists from included articles published from 2000-2019. Thirteen quantitative and five qualitative manuscripts were included which all focused on patient/family-perpetrated violence in outpatient physician clinics. No studies examined other violence types (e.g., worker-on-worker; burglary). The overall prevalence of Type II violence ranged from 9.5% to 74.6%, with the most common form being verbal abuse (42.1-94.3%), followed by threat of assault (14.0-57.4%), bullying (2.5-5.7%), physical assault, (0.5-15.9%) and sexual harassment/assault (0.2-9.3%). Worker consequences included reduced work performance, anger, and depression. Most workers did not receive training on how to manage a violent patient. More work is needed to examine the prevalence and risk factors of WPV in outpatient physician clinics for purposes of informing prevention efforts in these settings.

Background: Cirrhosis-associated immune dysfunction (CAID) contributes to high sepsis risk in patients with chronic liver disease. Various innate and; to a lesser extent; adaptive immune dysfunctions have been described as contributors to CAID leading to immune-paresis and impaired anti-microbial response in cirrhosis. In this study, we examined the phenotype of CD8 + T cells in chronic liver disease with the aim to evaluate changes that might contribute to impaired immune responses., Methods: Sixty patients with cirrhosis were prospectively recruited for this study. CD8 + T cells from peripheral blood, ascites and liver explants were characterized using flow cytometry and immunohistochemistry, respectively. The transcriptional signature of flow-sorted HLA-DR + CD8 + T cells was performed using Nanostring™ technology. HLA-DR + CD8 + T cells interactions with PBMCs and myeloid cells were tested in vitro., Findings: Peripheral CD8 + T cells from cirrhotic patients displayed an altered phenotype characterized by high HLA-DR and TIM-3 surface expression associated with concomitant infections and disease severity, respectively. Paired peritoneal CD8 + T cells expressed more pronounced levels of HLA-DR and PD-1 compared to peripheral CD8 + T cells. HLA-DR + CD8 + T cells were enriched in cirrhotic livers compared to controls. TIM-3, CTLA-4 and PD-1 levels were highly expressed on HLA-DR + CD8 + T cells and co-expression of HLA-DR and PD1 was higher in patients with poor disease outcomes. Genes involved in cytokines production and intracellular signalling pathways were strongly down-regulated in HLA-DR + CD8 + T cells. In comparison to their HLA-DR - counterparts, HLA-DR + CD8 + T cells promoted less proliferation of PBMCs and induced phenotypic and functional dysfunctions in monocytes and neutrophils in vitro., Interpretation: In patients with cirrhosis, CD8 + T cells display a phenotypic, functional and transcriptional profile which may contribute to CAID. FUND: This work was supported by Medical Research Council, the Rosetrees Charitable Trust, Robert Tournut 2016 grant (Sociéte Nationale Française de GastroEntérologie), Gilead® sciences, and NIHR Imperial Biomedical Research Centre., (Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.)

Liver transplantation (LT) is a successful treatment for patients with liver failure. However, organ shortage results in over 11% of patients losing their chance of a transplant attributed to liver decompensation (LD) and death. Ischemia/reperfusion injury (IRI) following conventional cold storage (CS) is a major cause of injury leading to graft loss after LT. Normothermic machine perfusion (NMP), a method of organ preservation, provides oxygen and nutrition during preservation and allows aerobic metabolism. NMP has recently been shown to enable improved organ utilization and posttransplant outcomes following a phase I and a phase III randomized trial. The aim of the present study is to assess the impact of NMP on reducing IRI and to define the underlying mechanisms. We transplanted and compared 12 NMP with 27 CS-preserved livers by performing gene microarray, immunoprofiling of hepatic lymphocytes, and immunochemistry staining of liver tissues for assessing necrosis, platelet deposition, and neutrophil infiltration, and the status of steatosis after NMP or CS prereperfusion and postreperfusion. Recipients receiving NMP grafts showed significantly lower peak aspartate aminotransferase (AST) levels than those receiving CS grafts. NMP altered gene-expression profiles of liver tissue from proinflammation to prohealing and regeneration. NMP also reduced the number of interferon gamma (IFN-γ) and interleukin (IL)-17-producing T cells and enlarged the CD4 pos CD25 high CD127 neg FOXP3 pos regulatory T cell (Treg) pool. NMP liver tissues showed less necrosis and apoptosis in the parenchyma and fewer neutrophil infiltration compared to CS liver tissues. Conclusion: Reduced IRI in NMP recipients was the consequence of the combination of inhibiting inflammation and promoting graft regeneration., (© 2018 by the American Association for the Study of Liver Diseases.)

Competing Interests: Conflict of interest The authors declare that there is no conflict of interest.

Background & Aims: Chronic infection with hepatitis B virus (HBV) progresses through different phases. The first, called the immune-tolerant phase, has been associated with a lack of disease activity. We examined HBV-DNA integration, clonal hepatocyte expansion, HBV antigen expression, and HBV-specific immune responses in patients in the immune-tolerant phase to assess whether this designation is appropriate or if there is evidence of disease activity., Methods: We studied HBV-DNA integration, clonal hepatocyte expansion, and expression of hepatitis B surface antigen and core antigen in liver tissues from 26 patients with chronic HBV infection (ages, 14-39 y); 9 patients were positive for hepatitis B e antigen (HBeAg) in the immune-tolerant phase and were matched for age with 10 HBeAg-positive patients with active disease and 7 HBeAg-negative patients with active disease. Peripheral blood samples were collected and HBV-specific T cells were quantified for each group., Results: Detection of HBV antigens differed among groups. However, unexpectedly high numbers of HBV-DNA integrations, randomly distributed among chromosomes, were detected in all groups. Clonal hepatocyte expansion in patients considered immune tolerant also was greater than expected, potentially in response to hepatocyte turnover mediated by HBV-specific T cells, which were detected in peripheral blood cells from patients in all phases of infection., Conclusions: We measured HBV-specific T cells, HBV-DNA integration, and clonal hepatocyte expansion in different disease phases of young patients with chronic hepatitis B, with emphasis on the so-called immune-tolerant phase. A high level of HBV-DNA integration and clonal hepatocyte expansion in patients considered immune tolerant indicated that hepatocarcinogenesis could be underway-even in patients with early stage chronic HBV infection. Our findings do not support the concepts that this phase is devoid of markers of disease progression or that an immune response has not been initiated. We propose that this early phase be called a high-replication, low-inflammation stage. The timing of therapeutic interventions to minimize further genetic damage to the hepatocyte population should be reconsidered., (Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Predicting survival in decompensated cirrhosis (DC) is important in decision making for liver transplantation and resource allocation. We investigated whether high-resolution metabolic profiling can determine a metabolic phenotype associated with 90-day survival., Methods: Two hundred and forty-eight subjects underwent plasma metabotyping by (1)H nuclear magnetic resonance (NMR) spectroscopy and reversed-phase ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry (UPLC-TOF-MS; DC: 80-derivation set, 101-validation; stable cirrhosis (CLD) 20 and 47 healthy controls (HC))., Results: (1)H NMR metabotyping accurately discriminated between surviving and non-surviving patients with DC. The NMR plasma profiles of non-survivors were attributed to reduced phosphatidylcholines and lipid resonances, with increased lactate, tyrosine, methionine and phenylalanine signal intensities. This was confirmed on external validation (area under the receiver operating curve [AUROC]=0.96 (95% CI 0.90-1.00, sensitivity 98%, specificity 89%). UPLC-TOF-MS confirmed that lysophosphatidylcholines and phosphatidylcholines [LPC/PC] were downregulated in non-survivors (UPLC-TOF-MS profiles AUROC of 0.94 (95% CI 0.89-0.98, sensitivity 100%, specificity 85% [positive ion detection])). LPC concentrations negatively correlated with circulating markers of cell death (M30 and M65) levels in DC. Histological examination of liver tissue from DC patients confirmed increased hepatocyte cell death compared to controls. Cross liver sampling at time of liver transplantation demonstrated that hepatic endothelial beds are a source of increased circulating total cytokeratin-18 in DC., Conclusion: Plasma metabotyping accurately predicts mortality in DC. LPC and amino acid dysregulation is associated with increased mortality and severity of disease reflecting hepatocyte cell death., (Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

We studied the effect of grape seed extract Burgund Mare (BM) on oral carcinogenesis and compared it with that of curcumin (CU). Wistar rats were divided into six groups (n = 10): 4-nitro-quinoline-1-oxide (4NQO) oral carcinogenesis was induced to groups 1 - 5; groups 2 and 3 received BM and CU respectively during initiation and groups 4 and 5 BM and CU during post-initiation of carcinogenesis; group 6 represented the negative control group. Total malondialdehyde (MDA) and reduced glutathione (GSH) were assayed fluorometrically in oral tissue (gingival, jugal, palatal, lingual mucosa) and serum. Histopathological exam was performed and a dysplasia score given to each oral mucosal lesion. Ki67, cyclin D1, p63, Bcl2 and p53 were immunohistochemically evaluated. BM and CU reduced tissue MDA values elevated by 4NQO (P = 0.000). The difference between CU and BM effect was significant in the initiation (P = 0.02) but not in the post-initiation phase of carcinogenesis (P = 0.58). Tissue GSH levels decreased by 4NQO (P < 0.001) were not significantly modified by BM or CU. Serum MDA levels increased by 4NQO (P = 0.000) were significantly lowered by CU (P = 0.04) and BM (P = 0.04) during initiation and by CU during post-initiation of carcinogenesis (P = 0.01). CU was more potent than BM during post-initiation of carcinogenesis (P = 0.01). Serum GSH lowered by 4NQO (P = 0.55) was significantly decreased by BM and CU (P < 0.012), with no significant difference between groups receiving BM or CU. Moderate dysplasia was the most advanced dysplasia induced and gingival localization the most frequent. Both BM and CU lowered dysplasia scores, with BM being the most efficient during post-initiation of carcinogenesis (P = 0.001). Ki67, cyclin D1, p63, Bcl2 and p53 expression increased with dysplasia scores. BM showed chemopreventive properties during initiation and post-initiation of oral carcinogenesis, reducing local and general oxidative stress and the intensity of dysplasia. During post-initiation of carcinogenesis BM and CU exhibited similar effects.

Purpose: The study aims to assess the correlation between stromal fibrillary component (SFC) and vascular density (VD) in Gleason architectural patterns of prostate carcinoma., Materials and Methods: 680 digital images of prostate adenocarcinoma labeled following both Gleason and Srigley systems were acquired with X20 objective from serial sections, one stained using Gömöri technique for SFC and one immunomarked with anti-CD34 antibody for vessels. The SFC amount and VD were determined and compared. Gleason patterns were divided in: "Solid" group (Gleason 3a, 3b, 4b, 5b) and "Necrotizing" group (Gleason 3c 4a and 5a). For each parameter were assessed: the lowest value (VMIN), the highest value (VMAX), the half range value (HRV), mean value (AV), standard deviation (STDEV), mean value + standard deviation (AV+ STDEV ) and mean value + standard deviation (AV+ STDEV). The Pearson product-moment correlation coefficient and the χ2 test were used., Results: The relationship between SFC and VD values had an inverse, descending correlation in Gleason 2 pattern and a direct, ascending correlation in Gleason 4 and 5 patterns. In Gleason 3 pattern, although the trend line had a direct ascending trend, it was not validated by the Pearson's and χ2 tests. However, SFC and VD values had a direct, ascending correlation for all determinations (p<0.05), but also for "Solid" (p<0.05) and "Necrotizing" (p<0.05) groups., Conclusions: The assessment of the relationship between the two main components of the intratumoral stroma in prostate carcinoma showed that they are evolving in a parallel manner. There is still need for studies on larger groups in order to decipher and more clearly define the way the stromal microenvironment is remodeling according to the malignant cell population degree of differentiation.

Outbreaks and pseudo-outbreaks of infection related to bronchoscopy typically involve Gram-negative bacteria, Mycobacterium species or Legionella species. We report an unusual bronchoscopy-related pseudo-outbreak due to Actinomyces graevenitzii. Extensive epidemiological and microbiological investigation failed to identify a common source. Strain typing revealed that the cluster was comprised of heterogeneous strains of A. graevenitzii. A change in laboratory procedures for Actinomyces cultures was coincident with the emergence of the pseudo-outbreak, and we determined that A. graevenitzii isolates more readily adopted a white, dry, molar tooth appearance on anaerobic colistin nalidixic acid (CNA) agar which likely facilitated its detection and identification in bronchoscopic specimens. This unusual pseudo-outbreak was related to frequent requests of bronchoscopists for Actinomyces cultures combined with a change in microbiology laboratory practices., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

An accessory spleen (AS), or splenunculus, is a small nodule of splenic tissue found outside of the spleen. Post-mortem examinations, also known as autopsies, are carried out to identify a cause of death, and to assess the state of the organs of the deceased. We present two incidental cases of splenunculi, one localized in greater omentum and a second one localized in the hilum of the spleen, diagnosed during a histopathological examination. An immunohistochemical profile of the normal and accessory spleen was followed where the expression of the CD20, CD3, CD23, α-SMA were analyzed.

Endometriosis is a benign disease defined by the presence of endometrial glands and stroma outside of the uterus and is associated with both pelvic pain and infertility. The most common sites of endometriosis, in decreasing order of frequency, are the ovaries, anterior and posterior cul-de-sac, posterior broad ligaments, uterosacral ligaments, uterus, fallopian tubes, sigmoid colon, appendix, and round ligaments. The main treatment is surgical, but often-microscopic islands of endometrial tissue remain, which proliferate and are responsible for relapses. We tested the efficacy of two drugs (Medroxyprogesterone and Triptorelinum), administered for six months to prevent recurrence after surgery. Treatment with Medroxyprogesterone was 100% effective in terms of relapse, while Triptorelinum could not prevent recurrence of endometriosis.

The authors made a preliminary assessment of possible correlations between the intratumoral vascular density (IVD) and the architectural tumoral patterns described by Gleason. The studied material consisted of samples obtained by transurethral resection from 34 patients diagnosed with prostatic adenocarcinoma. Ten fields, five for dominant and five for secondary identified patterns of each case, with no necrosis were selected randomly from CD34 immunomarked sections using ×20 objective. IVD increased with Gleason pattern both for the entire group, but also for "solid" phenotype group of subtypes up to pattern 4, respectively subtype 4B. In "necrotizing" phenotype group of subtypes, IVD had a decreasing trend from the better-differentiated subtypes to the poorest one. These preliminary data showed that the intratumoral vascular network reacts differently to the loss of tumoral differentiation in the two groups of Gleason subtypes suggesting the existence of two different populations of malignant cells.

Introduction: EML4-ALK fusion gene, is found in 3 to 5 % of lung adenocarcinoma and can be targeted by tyrosine-kinase inhibitor (TKI) with impressive therapeutic results., Case Report: We report the case of a non-smoking 40-year-old woman, diagnosed with metastatic poorly differentiated papillary adenocarcinoma of the lung harbouring the ALK fusion gene. After six cycles of first line chemotherapy with cisplatine-vinorelbine followed by maintenance treatment with erlotinib, the patient achieved a partial response. After disease progression, the patient was included in a trial comparing crizotinib with a classic 2nd line chemotherapy. After 1 month of crizotinib, the patient's condition improved. CT of the chest showed a near-total regression of bilateral pulmonary nodules replaced by pulmonary cysts., Conclusion: We report in this case a dramatic improvement with near-complete vanishing of pulmonary nodules replaced by pulmonary cysts in a patient treated with crizotinib. This case reminds us of the potential importance of evaluating the molecular diagnosis in lung cancers and especially in adenocarcinoma of the lung., (Copyright © 2012 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Emergence of drug-resistant bacteria represents a high, unmet medical need, and discovery of new antibacterials acting on new bacterial targets is strongly needed. ATP synthase has been validated as an antibacterial target in Mycobacterium tuberculosis, where its activity can be specifically blocked by the diarylquinoline TMC207. However, potency of TMC207 is restricted to mycobacteria with little or no effect on the growth of other Gram-positive or Gram-negative bacteria. Here, we identify diarylquinolines with activity against key Gram-positive pathogens, significantly extending the antibacterial spectrum of the diarylquinoline class of drugs. These compounds inhibited growth of Staphylococcus aureus in planktonic state as well as in metabolically resting bacteria grown in a biofilm culture. Furthermore, time-kill experiments showed that the selected hits are rapidly bactericidal. Drug-resistant mutations were mapped to the ATP synthase enzyme, and biochemical analysis as well as drug-target interaction studies reveal ATP synthase as a target for these compounds. Moreover, knockdown of the ATP synthase expression strongly suppressed growth of S. aureus, revealing a crucial role of this target in bacterial growth and metabolism. Our data represent a proof of principle for using the diarylquinoline class of antibacterials in key Gram-positive pathogens. Our results suggest that broadening the antibacterial spectrum for this chemical class is possible without drifting off from the target. Development of the diarylquinolines class may represent a promising strategy for combating Gram-positive pathogens.

Dilated cardiomyopathy is a major cause of heart failure and a major cause of morbidity and mortality. It is a multifactorial disease that includes both hereditary and acquired forms. It is estimated that around 20-35% of patients with dilated cardiomyopathy have hereditary forms. It is the third most common cause of heart failure and the most common cause of heart transplant. Dilated cardiomyopathy can be a secondary condition of many diseases such as coronary heart disease, diabetes, pheochromocytoma, infections, malnutrition, ingestion of toxic substances (alcohol, cocaine), ingestion of chemotherapeutic drugs, autoimmune diseases. In our study, we aimed to describe the changes of myocardial cells and interstitial connective tissue in patients clinically diagnosed with alcoholic dilated cardiomyopathy. The material studied consisted of heart fragments sampled from the left ventricle (LV) during necropsy from a total of 28 patients, aged between 58 and 73 years, with a clinical and laboratory diagnosis of dilated cardiomyopathy, hospitalized in the Cardiology Center of the Emergency County Hospital of Craiova in 2009 and 2010. In dilated cardiomyopathy, myocardial muscle fibers appeared slightly elongated or wavy, with hypochromatic, heterogeneous, vacuolar sarcoplasm, by a decrease of myofibril numbers. Lipofuscin granules were frequently seen in the sarcoplasm. Nuclear changes were consistent with sarcoplasmic alterations. Changes of the interstitial connective tissue were sometimes extensive and sometimes barely noticeable. The most common alteration of this structure was the onset and development of a mainly perivascular collagen fibrillogenetic process.

Avascular necrosis of the femoral head is an illness with a controversial etiology, the trigger event being the suppression of blood flow to the femoral head. The disease affects mostly young adults within their third and fifth decade, the majority of the patients being men. The main risk factors are trauma, chronic alcohol consumption, smoking, corticotherapy. The main goal of our study is to describe the morphometric changes found in the bone tissue of patients diagnosed with avascular necrosis of the femoral head, with different risk factors, by comparing the area of bone trabeculae inside the area of necrosis with that from the adjacent viable tissue. The morphometric study used biological material from 16 patients with ages between 29 and 57 years, who underwent surgery for avascular necrosis of the femoral head. They were admitted in the Orthopedics Department at the Emergency County Hospital in Craiova between 2010 and 2011 and were split into four groups. Group I presented trauma as the main risk factor, Group II had corticotherapy as the defining risk factor, Group III presented chronic alcohol consumption and Group IV was represented by the patients who smoked and exhibited chronic alcohol consumption. There was not a significant statistical difference between the areas of bone trabeculae of the four groups when we compared viable bone tissue to the necrotized one. Knowing the risk factors of the avascular necrosis of the femoral head is critical to the management of the disease, because diagnosing it in an early stage is a necessity for obtaining a good result for conservative treatment.

The authors made a preliminary assessment of possible correlations between the amount of intratumoral stromal fibrillary components (ISFC) and the architectural tumoral patterns described by Gleason. The studied material consisted of samples obtained by transurethral resection from 34 patients diagnosed with prostatic adenocarcinoma. Ten fields, five for dominant and five for secondary identified patterns of each case, with no necrosis were selected randomly from Gömöri stained sections using ×20 objective. ISFC-ratio increased with Gleason pattern both for the entire group but also for "Necrotizing" phenotype patterns and "Solid" phenotype patterns, excepting the subtype "4A" where the stromal compartment was reduced by the expansion of tumoral ducts enlarged by growing tumoral intraductal cribriform masses. These preliminary data showed that stromal microenvironment try to adapt to the loss of tumoral differentiation by increasing the amount of fibrillary components of intratumoral stromal compartment.

Chronic gastritis has a high incidence in adults, causing progressive destruction of glandular structures, favoring the development of gastric atrophy. The association of chronic gastritis with intestinal type metaplasia of gastric mucosa has a poor outcome as intestinal metaplasia is regarded as a precancerous lesion. Metaplasia is common in patients with Helicobacter pylori infection and also heavy smokers. The aim of our study was to evaluate the relationship between chronic gastritis and intestinal metaplasia. The study was conducted on a total of 1218 patients, aged between 5 and 90 years, who presented for dyspeptic disorders in the period 2007-2010 and were examined clinically and endoscopically. During the gastroscopic examination, fragments of gastric mucosa were collected for the histopathological study and for highlighting the H. pylori infection. For the histopathological study, the Hematoxylin-Eosin and PAS-Alcian Blue stains were performed, while for the immunohistochemical study the anti-TAG72 and anti-PCNA antibodies were used. A diagnosis of gastritis was established in 615 patients, representing approximately 50.5% of all cases. Most cases with gastritis were found in people of middle age. Gastritis was present in almost all age groups, from teenagers to the elders. Of the 615 cases of gastritis, urease test was positive in 353 patients, representing approximately 57.40% of all patients with gastritis. Histopathological examination identified the presence of intestinal metaplasia in 61.60% of patients with chronic gastritis, mostly complete metaplasia. PCNA immunohistochemistry revealed that cell proliferation processes are intensified in intestinal metaplasia. This study highlights the importance of chronic gastritis, intestinal metaplasia, and H. pylori infection in the etiopathogeny of gastric cancer.

We studied the clinical and histopathological changes in twenty-seven cases of acute ischemic stroke, aged between 65 and 75 years. All deaths occurred within 30 days after stroke. The aim of our study was to establish the clinical and histological correlations in acute ischemic stroke to detect prognostic factors. Brain lesions after acute stroke were observed in all regions. Our study describes the heterogeneity of brain injury after acute ischemic stroke with the participation of all brain components and the chronology in which these lesions develop and evolve. By histological and immunohistochemical studies, we identified neuronal, glial and vascular damage. The neurons had undergone in the area of lesion a process of necrosis, ballooning or condensation process. In the ischemic penumbra, we observed the presence of red neurons. Vascular lesions were represented by the discontinuity of capillaries, always associated with a marked perivascular edema. The following clinical and morphological correlations were established: liquefactive necrosis, astrocyte gliosis, phagocytosis phenomena are the more intense the later the death of the patient; apoptosis phenomena are the more intense the faster the death of the patient; the entire cerebral microcirculation presented microscopic modifications following the ischemic strokes, regardless of the time since the lesion occurred and the histological examination was made; the major neurological complications of the ischemic stroke - the hemorrhagic transformation phenomena, cerebral edema, were microscopically objectified, regardless of the time since the lesion occurred and the histological examination was made.

White adipose tissue from different locations is characterized by significant differences in the structure of adipocyte "secretoma". Fat accumulation in the central-visceral depots is usually associated with a chronic inflammatory state, which is complicated by the metabolic syndrome. Recently, the adipose tissue was emerged to have an essential role in the innate immunity, adipocytes being considered effector cells due to the presence of the Toll-like receptors (TLRs). In this study, we compared the expression of TNF-α, TLR2 and TLR4 in peripheral-subcutaneous and central-peritoneal adipose depots in three different conditions - lean, obese and obese diabetic - using immunohistochemistry. Our results suggest a correlation between the incidence of the stromal vascular cells and adipocytes TNF-α and TLR4 in the visceral depots in strong correlation with adipose tissue expansion. TLR2 positive cells were seen in the peripheral depots from all groups without any association with fat accumulation. These results focus on the existence of a new pathogenic pathway, the activation of TLR4, for the involvement of visceral adipose tissue in the activation and maintenance of the inflammatory cascade in obesity.