Unleashing Type-2 Dendritic Cells to Drive Protective Antitumor CD4+ T Cell Immunity.

Differentiation of proinflammatory CD4+ conventional T cells (Tconv) is critical for productive antitumor responses yet their elicitation remains poorly understood. We comprehensively characterized myeloid cells in tumor draining lymph nodes (tdLN) of mice and identified two subsets of conventional type-2 dendritic cells (cDC2) that traffic from tumor to tdLN and present tumor-derived antigens to CD4+ Tconv, but then fail to support antitumor CD4+ Tconv differentiation. Regulatory T cell (Treg) depletion enhanced their capacity to elicit strong CD4+ Tconv responses and ensuing antitumor protection. Analogous cDC2 populations were identified in patients, and as in mice, their abundance relative to Treg predicts protective ICOS+ PD-1lo CD4+ Tconv phenotypes and survival. Further, in melanoma patients with low Treg abundance, intratumoral cDC2 density alone correlates with abundant CD4+ Tconv and with responsiveness to anti-PD-1 therapy. Together, this highlights a pathway that restrains cDC2 and whose reversal enhances CD4+ Tconv abundance and controls tumor growth.

Exploring Perforated Jejunal GIST: A Rare Case Report and Review of Molecular and Clinical Literature.

This case report details a rare instance of a perforated jejunal gastrointestinal stromal tumor (GIST) in a 76-year-old female patient. The patient presented with acute abdominal pain and distension without any changes in bowel habits or episodes of nausea and vomiting. Initial diagnostics, including abdominal plain radiography and ultrasonography, were inconclusive; however, a computed tomography (CT) scan revealed pneumoperitoneum and an irregular fluid collection suggestive of small intestine perforations. Surgical intervention uncovered a 35 mm jejunal GIST with a 10 mm perforation. Histopathological examination confirmed a mixed cell type GIST with high malignancy potential, further substantiated by immunohistochemistry markers CD117, DOG1, and vimentin. Molecular analysis illuminated the role of key oncogenes, primarily KIT and PDGFRA mutations, emphasizing the importance of molecular diagnostics in GIST management. Despite the severity of the presentation, the patient's postoperative recovery was favorable, highlighting the effectiveness of prompt surgical and multidisciplinary approaches in managing complex GIST cases.

The Enigma of Mammaglobin: Redefining the Biomarker Paradigm in Breast Carcinoma.

The continuous evolution of cancer biology has led to the discovery of mammaglobin, a potential novel biomarker for breast carcinoma. This review aims to unravel the enigmatic aspects of mammaglobin and elucidate its potential role in redefining the paradigm of breast carcinoma biomarkers. We will thoroughly examine its expression in tumoral and peritumoral tissues and its circulating levels in the blood, thereby providing insights into its possible function in cancer progression and metastasis. Furthermore, the potential application of mammaglobin as a non-invasive diagnostic tool and a target for personalized treatment strategies will be discussed. Given the increasing incidence of breast carcinoma worldwide, the exploration of novel biomarkers such as mammaglobin is crucial in advancing our diagnostic capabilities and treatment modalities, ultimately contributing to improved patient outcomes.

A Rare Case Of Type II Amyand's Hernia.

Amyand's hernia represents an inguinal hernia containing an appendix within the hernia sac. This extremely rare condition occurs in approximately 1% of all inguinal hernias. This report describes the case of an 84-year-old male who presented with a right inguinal mass that intraoperatively turned out to be Amyand's hernia type-II with a gangrenous and perforated appendix. An appendectomy and peritoneal lavage were performed, followed by a hernioplasty where a modified Bassini repair was used. The patient fully recovered, and was discharged from the hospital on the fourth day. A non-reducible inguinal hernia containing a perforated appendix is a very rare emergency that requires immediate intervention to prevent abdominal sepsis. Therefore, while examining an inguinal hernia, the possibility of Amyand's hernia should always be considered.

Understanding stable Tl isotopes in industrial processes and the environment: A review.

In this review, a compilation of the current knowledge on stable thallium (Tl) isotopes (205Tl and 203Tl) in specific industrial processes, soils and plants is presented. An overview of the processes that may control Tl concentration and Tl isotope fractionation is compiled, while also overviewing the ability of Tl isotopic ratios to be used as a 'fingerprint' in source apportionment. Thallium isotopic compositions not only depend on their origin, but also on soil processes that may occur over time. One of the most important phases affecting the fractionation of stable Tl isotopes in soils (or sediments) was systematically identified to be specific Mn(III,IV)-oxides (mainly birnessite), due to their potential ability of oxidative Tl sorption, i.e., indicative of redox Tl reactions to be critical controlling factor. It has been established that the Brassica family is a hyperaccumulator of Tl, with clear demonstrations of Tl isotopic fractionation occurring up the translocation pathway. A clear pattern, so far, was observed with Tl isotopic compositions in plants grown on soils that were contaminated and those grown on uncontaminated soils, indicating the importance of the growing medium on Tl uptake, translocation, and isotopic fractionation.

PD-1 blockade induces responses by inhibiting adaptive immune resistance.

Therapies that target the programmed death-1 (PD-1) receptor have shown unprecedented rates of durable clinical responses in patients with various cancer types. One mechanism by which cancer tissues limit the host immune response is via upregulation of PD-1 ligand (PD-L1) and its ligation to PD-1 on antigen-specific CD8(+) T cells (termed adaptive immune resistance). Here we show that pre-existing CD8(+) T cells distinctly located at the invasive tumour margin are associated with expression of the PD-1/PD-L1 immune inhibitory axis and may predict response to therapy. We analysed samples from 46 patients with metastatic melanoma obtained before and during anti-PD-1 therapy (pembrolizumab) using quantitative immunohistochemistry, quantitative multiplex immunofluorescence, and next-generation sequencing for T-cell antigen receptors (TCRs). In serially sampled tumours, patients responding to treatment showed proliferation of intratumoral CD8(+) T cells that directly correlated with radiographic reduction in tumour size. Pre-treatment samples obtained from responding patients showed higher numbers of CD8-, PD-1- and PD-L1-expressing cells at the invasive tumour margin and inside tumours, with close proximity between PD-1 and PD-L1, and a more clonal TCR repertoire. Using multivariate analysis, we established a predictive model based on CD8 expression at the invasive margin and validated the model in an independent cohort of 15 patients. Our findings indicate that tumour regression after therapeutic PD-1 blockade requires pre-existing CD8(+) T cells that are negatively regulated by PD-1/PD-L1-mediated adaptive immune resistance.

Antimicrobial treatment in invasive infections caused by Gordonia bronchialis: systematic review.

Background: Corynebacterium, Nocardia, Rhodococcus, Mycobacterium, as well as Gordonia genera belongs to the genus Gordonia, Actinomycetia class. Gordonia bronchialis is a nitrate-reducing, urease-producing, non-motile, force aerobe with a rod-like figure that is known to arrangement into sessile, cord-like groups. This systematic review aimed to establish whether and what invasive infections in humans were caused by Gordonia bronchialis, and to evaluate outcomes of administered antibiotic treatment. Methods: We have registered this systematic review in PROSPERO database of systematic reviews and meta-analyses with the number CRD42022369974. Results: A total of 24 publications were included (22 case reports and two case series) with 28 individual cases. The oldest patients had 92 years, and the youngest patients had 13 years. Clinical signs of infection were present in six patients (21%). All isolates were susceptible to ciprofloxacin, imipenem, and amikacin. Vancomycin was the most frequently used antibiotic with nine cases followed by ciprofloxacin, ceftriaxone, and amoxicillin/clavulanic acid. Conclusion: Although there are no standardized recommendations to date, successful treatment with a favorable outcome has most often been carried out with fluoroquinolones, vancomycin with or without aminoglycosides, as well as carbapenems.

Small Bowel Perforation Due to Renal Carcinoma Metastasis: A Comprehensive Case Study and Literature Review.

This case report presents a unique instance of small bowel perforation caused by solitary metastasis from renal cell carcinoma (RCC), a rare and complex clinical scenario. The patient, a 59-year-old male with a history of RCC treated with nephrectomy four years prior, presented with acute abdomen symptoms. Emergency diagnostic procedures identified a significant lesion in the small intestine. Surgical intervention revealed a perforated jejunal segment due to metastatic RCC. Postoperatively, the patient developed complications, including pneumonia and multi-organ failure, leading to death 10 days after surgery. Histopathological analysis confirmed the metastatic nature of the lesion. This case underscores the unpredictable nature of RCC metastasis and highlights the need for vigilance in post-nephrectomy patients. The rarity of small bowel involvement by RCC metastasis, particularly presenting as perforation, makes this case a significant contribution to medical literature, emphasizing the challenges in the diagnosis and management of such atypical presentations.

Determination of physical properties of undisturbed soil samples according to V. Novák.

The methodology described here presents the procedures for determining physical soil properties of undisturbed soil samples. Besides describing the methods for determining bulk and particle density, moisture content and porosity of the soil in detail, it also offers a way of determining soil's water holding properties when there is no pressure membrane apparatus available. This method is based on a capillary water saturation experiment and gravimetric measurements performed in different time intervals after the saturation (30 minutes, 2 hours, and 24 hours). With a few, simple to follow steps, and not using complicated and space-consuming equipment, it can be replicated in almost any laboratory, and the results are easily interpreted. The method was, and still is, widely used in the Czech Republic, and some parts of it are used as standard soil testing methods. To a lesser or greater detail, this method is described in Rejsek (1999), Valla et al. (2011), Pospísilová et al. (2016) and ÚKZÚZ (2016), and this methodology is compiled from those publications, mainly focusing (and using the same abbreviations) on the procedures described by Valla et al. (2011). The methodology described does not essentially differ from the original, but the steps here have been described to a greater detail, based on the practical experiences obtained over the years, in order to make some common mistakes less likely to happen. The methodology is further complemented with graphical illustrations for each step described in the process, making it clearer, more easily understood, and easier to replicate. Since this methodology has not been available in English so far, this guide offers a great opportunity of its replication on an international level.•Simple, cost-effective and environmentally friendly method for determining physical soil properties•Easy replication and results interpretation•Results can be obtained even in non-highly specialized soil laboratories.

The Emerging Roles of the Adaptive Immune Response in Acute Pancreatitis.

Acute pancreatitis (AP) is an abrupt, variable inflammatory condition of the pancreas, potentially escalating to severe systemic inflammation, rampant pancreatic necrosis, and multi-organ failure. Its complex pathogenesis involves an intricate immune response, with different T cell subsets (Th1, Th2, Th9, Th17, Th22, TFH, Treg, and CD8+ T cells) and B cells playing pivotal roles. Early T cell activation initiates the AP development, triggering cytokines associated with the Th1 response, which stimulate macrophages and neutrophils. Other T cell phenotypes contribute to AP's pathogenesis, and the balance between pro-inflammatory and anti-inflammatory cytokines influences its progression. Regulatory T and B cells are crucial for moderating the inflammatory response and promoting immune tolerance. B cells further contribute through antibody production, antigen presentation, and cytokine secretion. Understanding these immune cells' roles in AP could aid in developing new immunotherapies to enhance patient outcomes. However, further research is required to define these cells' precise roles in AP and their potential as therapeutic targets.

Secondary Breast Malignancy from Renal Cell Carcinoma: Challenges in Diagnosis and Treatment-Case Report.

Renal cell carcinoma represents about 2% of all malignant tumours in adults. Metastases of the primary tumour in the breast make up to about 0.5-2% of the cases. Renal cell carcinoma metastases in the breast are extremely rare and have been sporadically recorded in the literature. In this paper, we present the case of a patient with breast metastasis of renal cell carcinoma 11 years after primary treatment. Case presentation: An 82-year-old female who had right nephrectomy due to renal cancer in 2010 felt a lump in her right breast in August 2021, whereby a clinical examination revealed a tumour at the junction of the upper quadrants of her right breast, about 2 cm, movable toward the base, vaguely limited, and with a rough surface. The axillae were without palpable lymph nodes. Mammography showed a circular and relatively clearly contoured lesion in the right breast. Ultrasound showed an oval lobulated lesion of 19 × 18 mm at the upper quadrants, with strong vascularisation and without posterior acoustic phenomena. A core needle biopsy was performed, and the histopathological findings and obtained immunophenotype indicated a metastatic clear cell carcinoma of renal origin. A metastasectomy was performed. Histopathologically, the tumour was without desmoplastic stroma, comprising predominantly solid-type alveolar arrangements of large moderately polymorphic cells, bright and abundant cytoplasm, and round vesicular cores with focally prominent nuclei. Immunohistochemically, tumour cells were diffusely positive for CD10, EMA, and vimentin, and negative for CK7, TTF-1, renal cell antigen, and E-cadherin. With a normal postoperative course, the patient was discharged on the third postoperative day. After 17 months, there were no new signs of the underlying disease spreading at regular follow-ups. Conclusion: Metastatic involvement of the breast is relatively rare and should be suspected in patients with a prior history of other cancers. Core needle biopsy and pathohistological analysis are required for the diagnosis of breast tumours.

Antimicrobial Treatment of Serratia marcescens Invasive Infections: Systematic Review.

Background: Serratia marcescens (SM) is a Gram-negative pathogen discovered by Italian pharmacist, Bizio, in 1819. According to the literature, S. marcescens is resistant to a wide range of antibiotics, including penicillin, cephalosporin, tetracycline, macrolide, nitrofurantoin, and colistin. We conducted a systematic review of published reports, determined what invasive infections could cause SM, and established the most appropriate antibiotic therapy. Methods: We registered this systematic review on the PROSPERO registry of systematic reviews-meta-analyses before we started our research (registration number CRD42022323159). The online searches of published studies were implemented via MEDLINE, the Cochrane Central Register of Controlled Trials, EBSCO, Scopus, Google Scholar, SCIndex, and the registry of clinical studies of human participants (ClinicalTrials.gov). Results: Our study included 32 published articles (9 case series and 23 case reports). There were 57 individual cases, respectively. The oldest patient was 97 years and the youngest patient was a newborn. S. marcescens was, in most cases, isolated from blood followed by urine and cerebrospinal fluid. In most cases, sensitivity was tested to cotrimoxazole (from 27 isolates, 10 showed resistance) followed by gentamicin (from 26 isolates, 3 showed resistance) as well as amikacin (from 21 isolates, none showed resistance). Patients died from an infection in 21 cases (31%). Conclusions: Treatment of SM infections should include carbapenems or aminoglycosides in combination with third-generation (and eventually fourth-generation) cephalosporin. Cotrimoxazole should be considered in cases of uncomplicated urinary infections.

Appendiceal Signet Ring Cell Carcinoma: An Atypical Cause of Acute Appendicitis-A Case Study and Review of Current Knowledge.

Appendiceal signet ring cell carcinoma (ASRCC) is a rare and aggressive form of appendiceal cancer, often presenting with nonspecific symptoms that overlap with acute appendicitis. Early diagnosis and appropriate management are crucial for improving patient outcomes in these rare malignancies. This case report and literature review aims to raise awareness among clinicians about ASRCC of the appendix as a cause of acute appendicitis and highlight the importance of considering this diagnosis in patients with atypical presentations or unexpected histopathological findings. We present a 65-year-old female patient with ASRCC who underwent successful surgical treatment and remains disease-free at the one-year follow-up. It also highlights the necessity of early detection and appropriate treatment in order to improve patient outcomes. In addition, a comprehensive literature review is provided, discussing the clinical presentation, histopathological characteristics, potential pathogenesis, treatment options, and prognosis of ASRCC.

Burnout syndrome among medical nurse-technicians in intensive care units in cardiovascular surgery.

Background: Healthcare workers in intensive care units work under specifically hard conditions compared to healthcare workers who work under regular clinical conditions. In this sense, the research aims at assessing the level of burnout symptomatology among nurse technicians working in intensive care units for cardiovascular surgery and to compare those burnout levels with those recorded for medical technicians working under regular clinical conditions. Method: The research was designed as a cross-sectional study. The sample consisted of nurse technicians working in intensive care units specializing in cardiovascular surgery (70 participants) and nurse technicians working under regular clinical conditions (70 participants) at the Institute for Cardiovascular Diseases "Dedinje," Belgrade, Serbia. To evaluate the manifestation of burnout syndrome at work, the analysis uses the Serbian version of the Maslach Burnout Inventory-Human Services Survey (MBI-HSS). Results: To examine the variances in the average sub-scores for burnout within two groups of medical technicians, the study used Two Independent Samples T-test. The statistically noteworthy differentiation was ascertained for emotional exhaustion and personal accomplishment, but this does not hold true for depersonalization. However, the mean score values across the different burnout levels (low, moderate, high) are similar in two cohorts of respondents (p > 0.05). Conclusion: This study will serve as an impetus for a policy reform focused on ameliorating working conditions and improving healthcare workers' satisfaction and overall healthcare quality.

Metastatic Breast Cancer Presenting as Acute Appendicitis: A Rare Case Study and Review of Current Knowledge.

This manuscript discusses a rare case of acute appendicitis caused by metastasis from invasive breast carcinoma of no special type in a 70-year-old female previously diagnosed with breast cancer. It delves into the diagnostic challenges and management complexities of such unusual clinical presentations. The paper includes an analysis of 19 documented cases, enriching the understanding of metastatic patterns and treatment strategies in breast cancer. It underlines the importance of considering a history of malignancy when diagnosing acute abdominal conditions and emphasizes a comprehensive approach in interpreting diagnostic imaging in patients with past oncological issues to effectively manage metastatic breast cancer exhibiting atypical manifestations.

Assessment of potential exposure to As, Cd, Pb and Zn in vegetable garden soils and vegetables in a mining region.

Mining and smelting activities can contaminate soils and affect farming due to high emissions and input of potentially toxic elements (PTE) into the environment. Soils (sampled from two depths) and market vegetables from vegetable gardens located within the vicinity of unconfined slag deposits from decades of mining and smelting activities in Kutná Hora, Czechia were assessed to determine to what extent they pose a health hazard to communities that use these gardens. Pseudo-total As concentrations in the soils exceeded background levels (4.5 mg kg-1) 1.9-93 times, with higher concentrations in the deeper layer. The pseudo-total concentrations of PTE in soils ranked in the order As > Zn > Cd > Pb. Phyto-available concentrations of PTE in soils were relatively low, compared to pseudo-total concentrations. Concentration of As, Cd, Pb and Zn in the vegetables exceeded guideline values, with the highest concentrations found in the fruits of cucumber, peppers, and zucchini. Despite low phyto-available PTE concentrations in soils, all the PTE concentrations in the vegetables surpassed the guidelines set by the Czech Ministry of Health and EU directive, indicating a health hazard to consumers.

Effect of peat organic matter on sulfide weathering and thallium reactivity: Implications for organic environments.

Weathering of Tl-containing sulfides in a model (12-week) peat pot trial was studied to better understand their geochemical stability, dissolution kinetics, alteration products and the associated release and mobility of anthropogenic Tl in organic environments. We also present the effect of industrial acid rainwater on sulfide degradation and Tl migration in naturally acidic peat. Sphalerite (ZnS) was much less stable in peat than other Tl-containing sulfides (galena and pyrite), and thus acted as a major phase responsible for Tl mobilization. Furthermore, Tl incongruently leached out over Zn from ZnS, and accumulated considerably more in the peat solutions (≤5 µg Tl/L) and the peat samples (≤0.4 mg Tl/kg) that were subjected to acid rain watering compared to a deionized H2O regime. This finding was in good agreement with the absence of secondary Tl-containing phases, which could potentially control the Tl flux into the peat. The behavior of Tl was not as conservative as Pb throughout the trial, since a higher peat mobility and migration potential of Tl was observed compared to Pb. In conclusion, industrial acid precipitations can significantly affect the stability of ZnS even in acidic peat/organic environments, making it susceptible to enhanced weathering and Tl release in the long term.

Lifestyle, Physical Activity, Eating and Hygiene Habits: A Comparative Analysis Before and During the COVID-19 Pandemic in Student Population.

Background: Changing daily habits such as diet, hygiene and physical activity may be some of the consequences of the COVID-19 pandemic. The aim of the study was to analyze the effect of this pandemic on lifestyle, physical activity, eating and hygiene habits among students. Methods: This cross-sectional study involved 171 students from the Faculty of Medical Sciences, University of Kragujevac, Serbia. Data were statistically analyzed using Wilcoxon Signed-Rank test, Marginal homogeneity test and Chi-square test. The differences were considered statistically significant when p ≤ 0.05. Results: In this study, it was observed that the most common physical activity before the pandemic was walking, while during the pandemic was home exercising. Compared to the period before the pandemic, there was no difference in the time spent engaging in daily physical activity (p = 0.334). However, there was a significant increase in sitting time during the pandemic (p = 0.005). Difference was noticed in the use of breakfast, the number of meals, and the type of fat in the diet before and during the pandemic (p = 0.000). During the pandemic, there was an increase in the use of fruits (p = 0.000), vegetables, and nuts (p = 0.001), while the use of fast food and alcohol have decreased. During the COVID-19 pandemic, a significant increase in the use of dietary supplements was observed (40.2%), (p = 0.008). Conclusions: Given that the COVID-19 pandemic is ongoing, certain changes in lifestyle observed in this study should be confirmed in more extensive population studies.

Validation of the fear of COVID-19 scale in a central Balkan country - Serbia.

Validation of the fear of introduction: High levels of fear of COVID-19 may be associated with increased levels of stress, anxiety, and depression, as well as decreased resilience and life expectancy. Objective: This study aimed to translate and confirm the Serbian version of the Fear of COVID-19 scale as well as to investigate its psychometric properties. Methods: The translation and intercultural adaptation of the Fear of COVID-19 scale was performed by the leading standard of the International Society for Pharmacoeconomics and Outcome Research. When the distribution was normal, the Kolmogorov-Smirnov test was used. The reliability of the Serbian version of FCV-19S was tested by measuring the internal consistency through the value of Cronbach's alpha. Results: The original version of the Fear of COVID-19 scale was tested on a sample of 256 subjects with a mean age of 25.38 ± 12.47. The Cronbach's alpha value was 0.864. We divided the scale by the split-half method (Spearman-Brown), and the value of the coefficient for the questionnaire as a whole was 0.882. Divergent criterion validity was tested through the non-parametric correlation between the scores of the Fear of COVID-19 scale and the Fear of Hospitalization scale. A score of the Fear of COVID-19 scale was calculated as the sum of each question for each of the respondents. Convergent criterion validity was tested through the non-parametric correlation between the scores of the Fear of COVID-19 scale and the Emotional Regulation Questionnaire. Conclusion: The validated version of the scale in Serbia complements versions available in other cultures and other languages and facilitates global studies related to mental health during the COVID-19 pandemic.

Resource Use and Costs Related to Hematological Complications of Chemotherapy: Cost of Illness Study Based on Data from Balkan Country with Recent History of Socioeconomic Transition.

Background: The administration of chemotherapy positively correlates with diverse adverse drug reactions, including the significant impact of hematological hazards such as anemia, leukopenia-neutropenia, thrombocytopenia, and pancytopenia. This pilot pharmacoeconomic study aimed to estimate the total direct costs of treating hematological toxicity induced by chemotherapy and its main determinants. Methods: The study was conducted as a retrospective cost of illness study using the "from bottom to the top" approach from the perspective of the Republic Health Insurance Fund. This study included 88 patients treated due to developing at least one episode of one of the types of hematological complications of cytostatics in 2018 at the Oncology Clinic of the University Clinical Center Kragujevac, Kragujevac, the Republic of Serbia. Results: Among cancer patients who developed haematological toxicity, treating pancytopenia was most demanding in a pharmacoeconomic manner compared to neutropenia and thrombocytopenia, with an estimated value of direct costs of 264,14, 178,19 and 157,76 euros per patient per year respectively. Regarding total direct costs, the main determinants were the costs of drugs, their parenteral administration, and costs due to hospitalization. Conclusion: Due to the rising cancer incidence and obligatory hospital treatment of hematological toxicity induced by chemotherapy, the identification of the pharmacoeconomic aspects of the treatment of these complications is needed. Future research should focus on the development of new modalities of treatment regarding patient characteristics anticipating high costs.