Cutaneous T-cell lymphomas (CTCLs), encompassing mycosis fungoides (MF) and Sézary syndrome (SS), present a complex landscape influenced by cytokines and cellular responses. In this work, the intricate relationship between these inflammatory proteins and disease pathogenesis is examined, focusing on what is known at a clinical and therapeutic level regarding the most well-known inflammatory mediators. An in-depth look has been given to their possible alterations caused by novel immunomodulatory drugs and how they may alter disease progression.From this narrative review of the actual scientific landscape, Interferon-gamma (IFN-γ) emerges as a central player, demonstrating a dual role in both promoting and inhibiting cancer immunity, but the work navigates through all the major Interleukins known in inflammatory environments.Immunotherapeutic perspectives are elucidated, highlighting the crucial role of the cutaneous microenvironment in shaping dysfunctional cell trafficking, antitumor immunity, and angiogenesis in MF, showcasing advancements in understanding and targeting the immune phenotype in CTCL.In summary, this manuscript aims to comprehensively explore the multifaceted aspects of CTCL, from the immunopathogenesis and cytokine dynamics centred around TNF-α and IFN-γ to evolving therapeutic modalities. Including all the major known and studied cytokines in this analysis broadens our understanding of the intricate interplay influencing CTCL, paving the way for improved management of this complex lymphoma.

Recent technological advances, including capsule endoscopy (CE) and balloon-assisted endoscopy (BAE), have revealed that small intestinal disease is more common than previously thought. CE has advantages including, high diagnostic yield, discom-fort-free, outpatient basis, and physiological images. BAE enabled endoscopic diagnosis and treatment in the deep small bowel. Computed tomography (CT) enterography with negative oral contrast can evaluate masses, wall thickening, and narrowing of the small intestine. In addition, Enhanced CT can detect abnormalities outside the gastrointestinal tract that endoscopy cannot evalu-ate. Each modality has its advantages and disadvantages, and a good combination of multiple modalities leads to an accurate diagnosis. As a first-line modality, three-phase enhanced CT is preferred. If CT shows a mass, stenosis, or wall thickening, a BAE should be selected. If there are no abnormal findings on CT and no obstructive symptoms, CE should be selected. If there are sig-nificant findings in the CE, determine the indication for BAE and its insertion route based on these findings. Early diagnosis of small intestinal tumors is essential for favorable outcomes. For early diagnosis, the possibility of small bowel lesions should be considered in patients with unexplained symptoms and signs after examination of the upper and lower gastro-intestinal tract.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause potentially life-threatening coronavirus disease (COVID-19). COVID-19 is a multisystem disease and is associated with significant respiratory distress, systemic hyper inflammation, vasculitis and multi-organ failures. SARS-CoV-2 causes deterioration of numerous systems with increasing evidence implying that COVID-19 affects endothelium and vascular function. The endothelium is important for preserving vascular tone and homeostasis. The overactivation and dysfunction of endothelial cells are significant outcomes of severity in patients with COVID-19. The Angiopoietin 1/Tie 2 pathway plays an important role in endothelium quiescence and vessel stability. The disruption of Angiopoietins/Tie balance affects vessel contact barrier and leads to vessel leakage, and this in turn causes endothelial dysfunction. Although vascular instability through SARS-CoV-2 is associated with endothelial dysfunction, it is still not understood if the virus affects Angiopoietin/Tie axis directly or via other mechanisms such as cytokine storm and/or immune response associated with the infection. This review provides an overview of the impact SARS-CoV-2 has on endothelial function and more specifically the Angiopoietin/Tie pathway.

This study explores the potential of natural compounds, including Daidzin, Luteolin, and Silibinin, as inhibitors of human monoamine oxidase B (MAO-B) for the treatment of Parkinson's disease. Docking simulations were performed using Autodock Vina with Pyrx program to evaluate the binding affinities of these compounds with MAO-B. Results indicate that Daidzin, Luteolin, and Silibinin exhibit promising binding affinities with MAO-B, with Daidzin demonstrating the highest affinity. Toxicity parameters were further predicted using the PkCSM Server, confirming the low toxicity of these compounds. Overall, the findings suggest that Daidzin, Luteolin, and Silibinin have the potential to be effective and safe treatments for Parkinson's disease through their inhibition of MAO-B. Further experimental validation is warranted to support their therapeutic efficacy in clinical settings.

Abstract Purpose Despite a considerable amount of literature on dual-energy-CT(DECT) iodine uptake of the head and neck, the physiologic iodine uptake of this region has not been defined yet. This study aims to establish reference values for the iodine uptake of healthy organs to facilitate clinical application. Material and Methods: Consecutive venous DECT scans of head and neck were reviewed, and unremarkable exams were included (n=617). 35 region of interest measurements were performed in 16 anatomical regions. Iodine uptake was compared among different organs/tissues and subgroup analysis was performed (male [n=403] vs female [n=214]; young [n=207] vs middle-aged [n=206] vs old [n=204]; normal weight [n=314] vs overweight [n=196] vs obese [n=107]]). Results: Overall mean iodine uptake values ranged between 0.5 and 9.4mg/ml. Women showed higher iodine concentration in the cervical vessels and higher uptake for the parotid gland, masseter muscle, submandibular glands, sublingual glands, palatine tonsils, tongue body, thyroid gland, and the sternocleidomastoid muscle than men (p0.04). With increasing age, intravascular iodine concentrations increased as well as iodine uptake for cerebellum and thyroid gland, while values for tongue and palatine tonsils were lower compared to younger subjects (p0.03). Iodine concentrations for parotid glands and sternocleidomastoid muscles decreased with higher BMI (p0.004), while normal-weighted patients showed higher iodine values inside the jugular veins, other cervical glands, and tonsils versus patients with higher BMI (p0.04). Conclusion: Physiologic iodine uptake values of cervical organs and tissues show gender-, age-, and BMI-related differences, which should be considered in clinical routine of head and neck DECT.

Cardiotoxicity is an unwanted side-effect arising from different medications. The term describes a diminution of heart function, affecting especially left ventricular ejection fraction, which can progress to heart failure. Pediatric oncology patients treated with drugs of the anthracycline group, e.g., doxorubicin, can evolve to heart failure patients in adult age. Nuclear Medicine imaging of fatty acid oxidation and glycolysis accurately describes normal and altered heart metabolism. The most common finding is a state of cardiac glycolysis, which is reflected by increased uptake of 18F-desoxyglucose (18F-FDG) at a time when fatty acid oxidation is decreased. Glycolysis has recently been recognized as being the result of coenzyme Q10 deficiency as part of adaptation to hypoxia. Low LEVF correlates with impaired fatty acid oxidation. This deficiency can arise from chemotherapy and radiation and can be corrected by supplementation. Drugs like enalapril can improve fatty acid utilization. We will review relevant Nuclear Medicine imaging studies as well as fundamental biochemical data that demonstrate this pathogenetic path.

The study focused on Molecular Docking simulations using Autodock Vina in conjunction with the Pyrx program to investigate potential drugs and natural compounds against the Bcr-Abl oncoprotein. From initial virtual screening of 200 compounds, 11 potential candidates were selected for further evaluation. Additional investigations included toxicity prediction using the pKCSM server. Among the compounds, Diosmin and Hesperidin showed high maximum tolerated doses in humans and low toxicity. Conversely, only Eltrombopag among the selected drugs exhibited excellent parameters, albeit with a potential risk of liver damage at high dosages. These findings underscore the need for comprehensive evaluation of efficacy and safety in the development of potential treatments targeting the Bcr-Abl oncoprotein.

Background: This study explores the impact of a gluten-free diet (GFD) on regional gastrointestinal (GI) transit times in individuals with celiac disease (CD) and non-celiac gluten sensitivity (NGCS). While a GFD is established for managing CD and wheat allergy, its effects on NGCS remain controversial due to inconclusive evidence. Methods: Utilizing a wireless motility and pH capsule (WMC) to assess regional and whole gut transit, newly diagnosed CD (n=12) and NGCS (n=12) patients underwent baseline evaluations, including measurements of gastric, small bowel, and colonic transit times. Results: At baseline conditions, individuals diagnosed with CD exhibited prolonged colonic and intestinal transit times when compared to those with NGCS (p<0.05). Following a 4-week GFD, CD patients experienced significant reductions in both intestinal and colonic transit times, along with enhanced small intestine contractility. NGCS individuals showed improvements in intestinal transit time and contractility with a GFD, although the colon exhibited no discernible effect. The GFD did not significantly impact intragastric, intestinal, or colonic pH. Conclusions: This study, employing WMC for the first time, provides novel insights into the positive effects of a GFD on intestinal and colonic transit, as well as contractility, in CD patients, and to a lesser extent, in those with NGCS.

Ionic liquid MIE-NH2 displays a new role of development of modification of glycoproteins of lactoferrin through a reductive amination mechanism to synthesize versatile pharmaceuticals. This work introduces a new strategy of modification of Lactoferrin by using methylimidazolium N-ethylamine, this ionic liquid MIE-NH2 linked to N-glycans in Lactoferrin derivatives. Using UPLC/ESI-QTOF and MALDI-TOF mass spectrometry to perform and detect the modifying of ionic liquid-linked glycoproteins. Relevantly, modifying the lactoferrin by MIE-H2 as a small molecule of ion liquid lactoferrin (IL-Lf), which could be a potential antiviral drug and it is achieved by inhibiting various targets. The probability of the lactoferrin modified as a small IL-Lf-molecule to inhibit any of these targets was investigated to find out its potency as a SARS-CoV-2 inhibitor. Molecular docking disclosed the activity of modifying glycoproteins - small IL-Lf-molecules containing amino groups and interaction with targeted Mpro, RdRp, TMPRSS2, and PLpro. Clinically, this study shows the a volubility to provide small IL-Lf-molecules as significantly important drugs that target main protease (Mpro), RNA dependent RNA polymerase (RdRp), transmembrane protease serine 2 (TMPRSS2), and Papain-like protease (PLpro).

Background: Granular cell tumor is a benign neurogenic tumor of the subcutaneous and submucosal area. The tongue is the most affected site of the oral cavity. The clinical presentation is non-specific and manifests as a submucosal nodule or mass. Because of its non-specific presentation, a definitive diagnosis an only be established after a histopathological examination and an immunohistochemical study to search for a neurogenic origin. Methods: We report the case of a 48-year-old man who was referred for the management of a nodular lesion on the tip of his tongue that had increased in size over the previous three months. Results: A complete surgical excision was performed for the histopathological exam, and an immunohistochemical study confirmed a strong expression of S100 and CD68. A diagnosis of granular cell tumor was confirmed. There was no recurrence et three years follow-up. Conclusion: the GCT is a rare tumor of nervous origin of the oral mucosa, it is non-specific in expression, with a good prognosis after complete excision. the histological and immunohistochemical diagnosis of the lesion is essential for the diagnosis.

The aging of the global population has increased the prevalence of neurodegenerative conditions. Bacopa monnieri (BM), an herb with active compounds, such as bacosides A and B, betulinic acid, loliolide, asiatic acid, and quercetin, demonstrates the potential for brain health. Limited research has been conducted on the therapeutic applications of BM in neurodegenerative conditions. This systematic review aims to project BM's beneficial role in brain disorders. BM has anti-apoptotic and antioxidant actions and can repair damaged neurons, stimulate kinase activity, restore synaptic function, improve nerve transmission, and increase neuroprotection. The included twenty-two clinical trials demonstrated that BM can reduce Nuclear Factor-κB phosphorylation, improve emotional function, cognitive functions, anhedonia, hyperactivity, sleep routine, depression, attention deficit, learning problems, memory retention, impulsivity, and psychiatric problems. Moreover, BM can reduce the levels of pro-inflammatory biomarkers and oxidative stress. Here, we highlight that BM provides notable therapeutic benefits and can serve as a complementary approach for the care of patients with neurodegenerative conditions associated with brain disorders. This review adds to the growing interest in natural products and their potential therapeutic applications by improving our understanding of the mechanisms underlying cognitive function and neurodegeneration and informing the development of new therapeutic strategies for neurodegenerative diseases.

Borderline Personality Disorder (BPD) is a complex and severe mental disorder. It is associated with greater use of medical services. It is characterized by intense fear of abandonment, recurring suicidal thoughts or self-harm, paranoid ideation or dissociation, identity difficulties, chronic feelings of emptiness, impulsive behavior and unstable moods and relationships. BPD is one of the most prevalent personality disorders with a higher diagnosis in females. For a diagnosis of BPD in patients, they must have a chronic pattern of functional impairment in addition to five of nine listed DSM-5 criteria. This review was a narrative literature search between 2000 to 2023 with a focus on BPD comorbidities. Results: Researchers observed a complex pattern of comorbidities with BPD that connects with other externalizing and internalizing disorders. BPD has a high comorbidity rate with mood disorders including bipolar I and II disorders, major depressive disorder, anxiety disorders, panic disorder alcohol use disorder, nicotine dependence, marijuana dependance, posttraumatic stress disorder, other personality disorders, binge eating disorder and ADHD. Diagnosis and management of BPD in presence of some of these disorders are discussed.

Enterococcus faecalis is a bacterial pathogen that can cause opportunistic infections. Studies indicate that initial biofilm formation plays a crucial regulatory role in these infections, as well as in colonising and maintaining the gastrointestinal tract as a commensal member of the microbiome of most land animals. It has long been thought that vegetation of endocarditis resulting from bacterial attachment to the endocardial endothelium requires some pre-existing tissue damage, and in animal models of experimental endocarditis, mechanical valve damage is typically induced by cardiac catheterisation preceding infection. This section reviews historical and contemporary animal model studies that demonstrate E. faecalis ability to colonise the undamaged endovascular endothelial surface directly and produce robust microcolony biofilms encapsulated within a bacterially derived extracellular matrix. This report reviews both previous and current animal model studies demonstrating the resilient capacity of E. faecalis to colonise the undamaged endovascular endothelial surface directly and produce robust microcolony biofilms encapsulated in a bacterially derived extracellular matrix. The article also considers the morphological similarities when these biofilms develop on different host sites, for example when E. faecalis colonises the gastrointestinal epithelium as a commensal member of the common vertebrate microbiome, lurking in plain sight and transmitting systemic infection. These phenotypes may enable the organism to survive as an unrecognised infection in asymptomatic subjects, providing an infectious resource for subsequent clinical process of endocarditis.

To better understand how immunity develops against SARS-CoV-2 during the pandemic period of 2020 to 2022, we analyzed the immune response of a small group of university staff and students who were either infected or vaccinated. We investigated the levels of receptor-binding domain (RBD)-specific and nucleocapsid (N)-specific IgG and IgA antibodies in serum and saliva samples taken early (around 10 days after infection or vaccination) and later (around 1 month later), as well as N-specific T-cell responses. One patient who had been infected in 2020 developed serum RBD and N-specific IgG antibodies, but declined 8 months later, then mRNA vaccination in 2021 produced a higher level of anti-RBD IgG than natural infection. In the vaccination of naïve individuals, vaccines induced anti-RBD IgG, but it declined after 6 months. A third vaccination boosted the IgG level again, albeit to a lower level than after the second. In 2022, when the Omicron variant became dominant, familial transmission occurred even among vaccinated people. In infected individuals, the levels of serum anti-RBD IgG antibodies increased later, while anti-N IgG peaked earlier. The N-specific activated T cells expressing IFN- or CD107a were detected early. In saliva, SARS-CoV-2-specific IgG but not IgA was detected. Interestingly, two individuals showed a temporary peak in RBD- and N-specific IgA antibodies in their saliva on the second day after infection. Thus, SARS-CoV-2 infection triggers typical immune responses in humans against acute viral infections, but mucosal immune responses, which are temporarily induced early during infection, may be more important for protection than current intramuscular vaccines.

Acute peritonitis is a severe complication of abdominal surgery with a high mortality rate. Intes-tinal insufficiency syndrome (IIS) is a key factor in the progression of peritonitis, contributing significantly to morbidity and mortality. The most characteristic and rapid manifestation of IIS is the development of intestinal paresis. Intestinal paresis is a condition characterized by inhibi-tion of intestinal motility, with the inability to evacuate intestinal contents. Intestinal paresis is caused by a cascade of neuroreflex and humoral reactions that lead to severe microcirculatory and metabolic disturbances. In the absence of adequate treatment, IIS can progress to enteritis, a state of complete intestinal insufficiency, with the inability to absorb nutrients and water.

Angiotensin-converting enzyme (ACE) inhibitors are used primarily in the treatment of hypertension, heart failure, and in the acute phase of myocardial infarction. Lisinopril [N2-[(1S)-1-car-boxy-3-phenylpropyl]-L-lysyl-L-proline], enalapril [(S)-1-[N-[1-(ethoxycarbonyl)-3-phenylpropyl]-L-alanyl]-L-proline] and ramipril [2-aza-bicyclo-[3.3.0]-octane-3-carboxylic acid] are all five-membered heterocycles and three of the most prevalent ACE inhibitors in clinical use worldwide. ACEi-induced angioedema (ACEi-AE) is clinically characterized by self-limited edema of the dermis and subcutaneous lipid tissue, localized on face skin, oral mucosa and tongue in most cases. However, severe episodes of intestinal AE misdiagnosed as acute appendicitis and laryngeal AE requiring incubation have been reported. The pathophysiology of ACEi induced-AE is attributed to the accumulation of bradykinin, which is a potent vasodilator with proinflammatory activity that is normally degraded by angiotensin-converting enzyme (ACE) and aminopeptidase P; however, a small proportion of treated patients is affected. Given that patients do not respond to anti-H1 antihistamines and steroids, the early clinical recognition and the ACEi discontinuation are the treatment of choice for the long term management of ACEi-AE.

This narrative review provides a thorough examination of medication-related osteonecrosis of the jaw (MRONJ), encompassing its etiology, the role of drug holidays, and contemporary treatment approaches. By systematically analyzing literature from 2022 to 2023, this paper synthesizes the latest findings and trends in MRONJ research. The study emphasizes the importance of a holistic understanding of MRONJ, beginning with its etiological factors, assessing the therapeutic implications of drug holidays, and evaluating the efficacy of current treatment modalities. This review aims to offer clinicians and researchers a consolidated resource, highlighting the intricacies of MRONJ management and proposing directions for future research. Through this comprehensive approach, the paper seeks to advance the understanding and treatment of MRONJ, ensuring an evidence-based, patient-centric approach in clinical practice.

Background: Auriculotherapy is a widely used approach for alleviating discomfort in patients experiencing pain, itchiness, sleep disturbances, and heightened anxiety. This method is also applicable to patients dealing with significant burn scars, who often encounter similar symptoms. Employed as an adjuvant therapy, auriculotherapy demonstrates potential in mitigating these clinical manifestations among individuals with major burn scars. These symptoms are known to be influenced by the autonomic nervous system. Objectives: Despite the absence of current data elucidating the impact of auriculotherapy on the autonomic nervous system, we embarked on an analysis of our heart rate variability (HRV) data to evaluate autonomic system functionality before and after the administration of auriculotherapy. Methods: Paired-samples t-tests and linear regression analysis of HRV variables and correlations with TBSA before and after auriculotherapy of a cohort of 31 survivors from 2016 Formosa Color Dust Explosion was carried out. Results: Significant change of specific HRV variables were found before and after auriculotherapy, and significantly negative correlations was revealed between TBSA and pre-SD prior to auriculotherapy. Conclusion: Our study showed that auriculotherapy may, at least in part, restore the equilibrium of autonomic nervous system and improve HRV parameters.

Background and Objectives: Place the question addressed in a broad context and highlight the purpose of the study. Materials and Methods: Describe briefly the main methods or treatments applied, including the study population description. Results: Summarize the article’s main findings. Conclusions: Indicate the main conclusions or interpretations. The abstract should be an objective representation of the article, it must not) results. Meanwhile, exclusion criterion is incomplete data in medical record. For the analysis of continuous variables, a General Linear Model (univariate) was employed, with the predictors included specific Personality Disorder. The outcome being the PB, and covariates encompassed age, sex, education, clinical diagnosis, and depression score. Results: Six personality disorders, namely Paranoid, Schizoid, Histrionic, Avoidant, Dependent, and Obsessive-Compulsive Personality Disorder, did not exhibit significant pathogenic beliefs. In contrast, the remaining four personality disorders demonstrated significant associations with specific pathogenic beliefs. Conclusions: While some personality disorders have specific beliefs, it's also common to have pathogenic beliefs that are not specific to their psychodynamic. It's essential to recognize specific pathogenic beliefs for each individual to be targeted for their psychotherapy.

Ovarian cancer poses a significant therapeutic challenge owing to the lack of specific targets for treatment. New treatment strategies are needed to improve patient outcomes and reduce the toxicity of existing therapies. This study aimed to investigate the synergistic effects of recombi-nant human apurinic/apyrimidinic endonuclease 1/redox factor 1 (rhAPE1/Ref-1) and aspirin on PEO14 and CAOV-3 ovarian cancer cells and human umbilical vein endothelial cells (HUVECs). Specifically, this study examined the mechanisms underlying the effect of rhAPE1/Ref-1 and as-pirin on cell death and the associated pathways. Cell viability was assessed using the MTT assay, and flow cytometry analysis and caspase-3/7 activity assays were conducted to determine apop-tosis. Western blotting was performed to evaluate the cleavage of poly(ADP-ribose) polymerase (PARP). Exposure to aspirin (3 mM) for 24 h did not affect cell viability in PEO14. Co-incubation of aspirin with rhAPE1/Ref-1 in PEO14 cells led to rhAPE1/Ref-1 acetylation and intracellular hyperacetylation. Co-treatment with aspirin (3 mM) and rhAPE1/Ref-1 induced a rhAPE1/Ref-1 concentration-dependent increase in cell death, particularly in PEO14 cells, as well as apoptosis, caspase-3/7 activation, and PARP cleavage. Furthermore, this combination treatment significantly increased paclitaxel-induced PEO14 cell death. Therefore, co-administration with rhAPE1/Ref-1 and aspirin is a potential strategy for ovarian cancer treatment.

Background: Exercise is an accepted intervention to improve the quality of life (QoL) of breast cancer patients. Exercise programs have been developed and all have shown satisfactory results in improving QoL. There is a lack of research comparing different prescription modalities. The aim of this study is to evaluate the effectiveness of physical exercise (in-person, home-based, prescription) on QoL in breast cancer patients actively undergoing treatment; Methods Quasi-experimental study with randomized assignment to three groups (in-person: guided and supervised in-person exercise program; home-based exercise: guided and supervised exercise program with streaming monitoring; recommendation: exercise recommendation). Quality of life was measured using the QLQ-C30 questionnaire. Baseline and 24-week analysis. Results: The total sample analyzed was n=80. QoL improved significantly at 24 weeks in the face-to-face and home-based exercise groups, but not in the advice group. Exercise in all modalities improved fatigue, nausea, vomiting, appetite, and constipation. QoL at 24 weeks depended on active chemotherapy, tumor type, and assigned exercise group (r2 = 0.503; p < 0.001). Conclusions: QoL in breast cancer patients undergoing active treatment improves after a 24-week exercise program, especially in face-to-face and home-based exercise. Home-based exercise, streaming-based recommendation is a viable option for exercise recommendation.

Food allergies are common worldwide and have become a major public health concern; more than 220 million people are estimated to suffer from food allergies worldwide. On the other hand, polyphenols, phenolic substances found in plants, have attracted attention for their health-promoting functions, including their anti-allergic effects. In this study, we examined the potential inhibitory effects of 80% ethanol extracts from 22 different vegetables on the degranulation process in RBL-2H3 cells. Our aim was to identify vegetables that could prevent and treat type I allergic diseases. We found strong inhibition of degranulation by the extracts of perilla and chives. Furthermore, we verified the respective efficacy via animal experiments, which revealed that the anaphylactic symptoms caused by ovalbumin (OVA) load were alleviated in OVA allergy model mice that ingested vegetable extracts of perilla and chives. These phenomena were suggested to be caused by induction of suppression in the expression of subunits that constitute the high-affinity IgE receptor, particularly the α-chain of FcεR I. Notably, the anti-allergic effects of vegetables that can be consumed daily are expected to result in the discovery of new anti-immediate allergenic drugs based on the components of these vegetables.

Tumor immunotherapy represented by immune target blocking and chimeric antigen receptor cell therapy has developed rapidly. Among them, Natural Killer Cell (NK) is gradually becoming another preferred immunotherapy method after T cell immunotherapy because of its unique killing effect in innate immunity and adaptive immunity. Although NK cell therapy has achieved promising results in clinical trials, there are still some problems, such as low efficacy in solid tumors, insufficient penetration of NK cells and high cost of treatment. Nanomaterials are expected to be an excellent tool to improve the anti-tumor immune response of NK cells due to their advantages such as chemical specificity, biocompatibility and simple synthesis. Nanomaterials can enhance the cytotoxicity of NK cells, participate in the modification and noninvasive cell-tracking patterns of NK cells，and mediate their homing and infiltration, and thus significantly improve the efficiency of NK cell immunotherapy. In this review, we will briefly introduce the methods and mechanisms of tumor immunotherapy, emphasize the research progress of NK cell-based immunotherapy and imaging, and finally summarize the direction and research progress of nanomaterials in NK cell-based immunotherapy.

The prognosis of cancer patients has greatly improved in the last years, owing to the development of novel chemotherapeutic agents. However, this progress comes with an increasing occurrence of cardiovascular adverse reactions. A serious side effect is arterial hypertension, which is the most frequent comorbidity encountered in cancer patients, influencing the outcomes in cancer survivors. Even though secondary hypertension related to specific chemotherapeutic agents, such as vascular endothelial growth factor inhibitors, is usually mild and reversible, in rare instances it can be severe, leading to discontinuation of chemotherapy. In addition, hypertension per se has been studied as a potential risk factor for cancer development. The relationship is even more complex than previously thought, as concerning evidence recently highlighted the potential oncogenic effects of antihypertensive drugs, such as thiazide diuretics predisposing to skin cancer. As a result, under the light of the similar risk factors and overlapping pathophysiological mechanisms between hypertension and cancer, a promising concept of onco-hypertension has emerged, aiming to improve the understanding of the complicated interplay between these two pathologies and maintain a balance between the efficacy and risks of both antihypertensive drugs and chemotherapy agents.

Nanotechnology has provided an opportunity for unparalleled development of the treatment of various severe diseases. The unique properties of nanoparticles offer a promising strategy in enhancing antitumor immunity by enhancing immunogenicity and presentation of tumor autoantigens for cancer immunotherapy. Polymeric, liposomal, carbon or silica-based nanoparticles are among those with major immunomodulatory roles in various cancer treatments. Cancer vaccines, in particular digestive cancer vaccines have been researched and developed on nanotechnological platforms. Due to their safety, controlled release, targeting of dendritic cells(DCs) and improved antigen uptake, as well as enhanced immunogenicity, nanoparticles have been used as carriers, as adjuvants for increased effect at the tumor level, for their immunomodulating effect, or for targeting tumor microenvironment, increasing tumor immunogenicity and reducing tumor inflamatory response. This review looks at digestive cancer vaccines developed on nanoparticle platforms and the impact nanoparticles have on the effects of these vaccines.

Zn2+ has been implicated in the regulation of intestinal redox and microbial homeostasis, and we recently reported that transient receptor potential canonical (TRPC) 6 channel activity contributes to intracellular Zn2+ homeostasis in mammalian cells. This study aims to investigate the role of TRPC6-mediated Zn2+ influx in stress resistance of intestine. Expression profile of TRPC1-C7 mRNAs in the actively inflamed mucosa from inflammatory bowel disease (IBD) patients was analyzed using GEO database. Systemic TRPC3-knockout (KO) and TRPC6-KO mice were treated with dextran sulphate sodium (DSS) to induce colitis. The Zn2+ concentration and the mRNA expression levels of oxidative/inflammatory markers in colon tissues were quantitatively analyzed, and gut microbiota profiles were compared. TRPC6 mRNA expression level was increased in IBD patients and DSS-treated mouse colon tissues. DSS-treated TRPC6-KO mice, but not TRPC3-KO mice, showed severe weight loss and increased disease activity index compared with DSS-treated WT mice. The mRNA abundances of antioxidant proteins were basically increased in TRPC6-KO colon, with changes in gut microbiota profiles. Treatment with TRPC6 activator prevented the DSS-induced colitis progression accompanied by increasing Zn2+ concentration. We suggest that TRPC6-mediated Zn2+ influx activity plays a key role in stress resistance against IBD, providing a new strategy for treating colitis.

Quercetin is a flavonoid with a low molecular weight that belongs to the human diet's phenolic phytochemicals and non-energy constituents. Quercetin has a potent antioxidant capacity, being able to capture Reactive Oxygen Species (ROS), reactive nitro-gen species (RNS), and Reactive Chlorine Species (ROC), which act as reducing agents by chelating transition metal ions. Its structure has five functional hydroxyl groups, which work as electron donors and are responsible for capturing free radicals. In addition to its antioxidant capacity, it was described different pharmacological properties of Quercetin, such as carcinostatic properties, antiviral, antihypertensive, anti-inflammatory, protection of Low-Density Lipoprotein (LDL) oxidation, and inhibi-tion of angiogenesis are developed in this review.

Objective: The study aimed to evaluate the effects of monoclonal antibodies (mAbs) acting on the calcitonin gene-related peptide (CGRP) or its receptor (anti-CGRP/R mAbs) on comorbid symptoms of depression, anxiety, and fatigue in migraine patients resistant to traditional prophylaxis. Methods: The study was an open-label prospective study assessing comorbidities in patients with high frequency (HFEM) and chronic migraine (CM), medication overuse headache (MOH), and resistance to traditional prophylaxis treated with anti-CGRP/R mAbs for 3 months. Results: 77 patients were enrolled with either HFEM (21%) or CM (79%) with or without MOH (56% and 44% respectively). We identified 21 non-responders (27%) and 56 responders (73%), defined on the reduction ≥ 50% of headache frequency. The two groups were highly homogeneous for investigated comorbidities. Disease severity in terms of headache frequency, migraine-related disability, and affective comorbid symptoms were reduced in both groups with different thresholds; allodynia and fatigue were ameliorated only in responders. Conclusion: anti-CGRP/R antibodies improve pain together with affection, fatigue, and sensory sensitization in migraine patients.

Introduction: Advanced glycation end-products (AGEs) may play a relevant role as inducers in the chronic inflammatory pathway present in immune-mediated diseases, such as systemic lupus erythematosus (SLE). AGEs concentrations have been associated, with discrepant results to date, with some parameters such as disease activity or accrual damage, suggesting their potential usefulness as biomarkers of the disease. Objectives: To confirm differences in AGEs levels measured by cutaneous autofluorescence between SLE patients and healthy controls (HC) and study their correlation with various disease parameters. Methods: Cross-sectional study, where AGEs levels were measured by skin autofluorescence, and SLE patients’ data were compared with those of sex- and age-matched HC in a 1:3 proportion through a multiple linear regression model. Correlations of AGEs levels with demographic and clinical data were analyzed through ANOVA tests. Both analyses were adjusted for confounders. Results: AGEs levels in SLE patients were significantly higher than in HC (p<0.001). We found statistically significant positive correlation with SLE disease activity index (SLEDAI) and damage index (SDI), physician and patient global assessment, C-reactive protein, leukocyturia, complement C4, IL6 and oral ulcers. We also found a negative statistically significant correlation with current positivity of anti-nuclear and anti-Ro60 antibodies. Conclusions: AGEs seem to have a role in LES pathophysiology, becoming a new management and prognosis biomarker in this disease. The association with specific antibodies and disease manifestations may indicate a specific clinical phenotype related to higher AGEs levels.

The lung microbiota is a complex community of microorganisms that colonize the respiratory tract of individuals from or even before birth. Although the lungs were traditionally believed to be sterile, recent research has shown that there is a diversity of bacterial species in the respiratory system. Knowledge about the lung microbiota in the newborn and its relationship with bacterial infections is of vital importance to understand the pathogenesis of respiratory diseases in neona-tal patients undergoing mechanical ventilation. In this article, the current evidence on the compo-sition of the lung microbiota in the newborn will be reviewed, as well as its role in the develop-ment of bacterial infections in mechanically ventilated neonates. Although advances in many as-pects of the neonatal intensive care unit care have significantly improved the survival of preterm infants, the diagnosis and treatment of ventilator-associated pneumonia has not progressed in recent decades. Avoiding dysbiosis caused by inappropriate use of antibiotics around birth, as well as avoiding intubation of patients or promoting early removal of endotracheal tubes are among the most important preventive measures for ventilator-associated pneumonia. The use of probiotics and prebiotics to prevent infectious, allergic or metabolic complications in the short or long term constitutes a very important field of research in perinatal medicine.

Physical exercise favorably affects visceral adipose tissue (VAT) which is a risk factor for cardiometabolic diseases. However, many people are unable or unwilling to conduct frequent and intensive exercise programs that have favorable effects on VAT. The present study aimed to determine the effect of the time-efficient and joint-friendly whole-body electromyostimulation (WB-EMS) technology on VAT volume in overweight to obese adults with osteoarthritis of the knee. In total 72 women and men 40-70 years old with femuro-tibial knee osteoarthritis were randomly allocated to WB-EMS (n=36) with 1.5 sessions of 20 min/week for 29 weeks or a usual care control group (CG: n=36) with 6 sessions of physiotherapy. Magnetic Resonance Imaging (MRI) using a non-contrast enhanced 2-point Dixon Gradient Echo Volumetric Interpolated Breath-hold Examination determined VAT. Twelve slices covered a total length of approximately 5 cm from mid L2 to mid L3. In summary, VAT volume increased non-significantly in the CG (p=.261) and decreased non-significantly in the WB-EMS group (p=.160). We failed to determine significant WB-EMS-induced effects i.e. group differences for absolute changes on VAT volume (p=.097). Due to the low application volume, present WB-EMS protocols might not be the perfect tool for decreasing VAT in overweight to obese adults.

Suicide is an important public health problem, fundamentally affecting the younger population and responding to multiple biological, psychological, and social causes. The objective of this study was to characterize changes suicide mortality, suicide methods and years of potential life lost during 2005 and 2019 in Paraguay. This observational, descriptive study used data from the Vital Statistics Information Subsystem of the Ministry of Public Health and Social Welfare. The average mortality rate from suicide was 4.9 per 100,000 inhabitants, with an increase from 4.2 between 200-2009 to 5.8 during 2014 and 2019. Suicide was more common in men (75%) than in women. In men, the highest mortality rate was observed among the 20-24 years-old whereas in women the age most affected were the 15–19-year-old age group. The most used method for suicide was strangulation. The most frequent places of suicide occurrence were at home (73%). The seasonality of suicide occurrence showed a slight increase in the spring-summer months compared with autumn winter (53% vs 47%). The rate of potential years of life lost statistically significantly increased from2005 to 2019. Public health measures need to be implemented to investigate the underlying reasons and to implement interventions in the population to decrease suicide mortality in Paraguay.

Mirror Therapy (MT) and Cognitive Therapeutic Exercise (CTE) are two neurorehabilitation techniques based on neuroplasticity and designed to enhance the functionality of the upper limb. Therefore, the aim is to assess the effectiveness of the combination of CTE and MT with task-oriented training (TOT) on fine and gross motor skills of the affected hand, as well as the functionality of the affected upper limb, autonomy, independence, and quality of life (QoL) in patients with acute stroke. This longitudinal and multicenter study involved a sample of 120 participants selected randomly and consecutively. Three groups were formed, including a control group (CG) and two treatment groups, one with MT and the other with CTE. The functionality of the upper limb, fine and gross motor skills, the quantity and quality of use of the affected upper limb, autonomy, and QoL were evaluated using various scales validated in the Spanish population at the baseline, after 20 treatment sessions, and at three months of follow-up. ANCOVA analysis was conducted, revealing statistically significant differences between assessments in the CG compared to the experimental groups (GEs), indicating a notable improvement in overall functionality, fine and gross motor skills, autonomy, and QoL in the latter. However, there were no significant differences between the GEs. Therefore, the application of either of these experimental combinations is crucial for the motor recovery, functionality, and improvement of the quality of life of individuals who have suffered a stroke.

Precise HDV-RNA detection and quantification are pivotal for accurate diagnosis and monitoring of response to newly approved treatment. We evaluate the performance of three assays: Hepatitis Delta RT-PCR system, EurobioPlex HDV assay, and the RoboGene HDV RNA Quantification kit 2.0, testing 151 HBsAg-positive samples, 90 HDV-RNA negative and 61 HDV-RNA positive. We also evaluated serial dilutions of the WHO international standard for HDV, PEI 7657/12. Finally, all HDV-RNA positive samples were genotyped using a next-generation sequencing strategy. Qualitative results indicated a 100% concordance between tests. Quantitative results correlated well between tests, r2=0.703 (Vircell-vs-Eurobio), r2=0.833 (Vircell-vs-RoboGene), r2=0.835 (Robogene-vs-Eurobio). Bias index was 2.083 (Vircell-vs-Eurobio), -1.283 (Vircell-vs-RoboGene), and -3.36 (Robogene-vs-Eurobio). Using the WHO IS, Vircell overestimated the viral load by 0.98 log IU/mL, Eurobio by 1.46 log IU/mL, and RoboGene underestimated it by 0.98 log IU/mL. Fifty-nine samples were successfully genotyped (Genotype 1, n=52; Genotype 5, n=7; Genotype 6, n=1), with similar results in terms of correlation and bias. The three assays demonstrate promising performance. Their accuracy, reflected in concordance rates and quantitative analysis, makes them suitable for clinical practice. However, in the absence of assay harmonization, quantitative HDV RNA monitoring should be performed in the same laboratory and assay to avoid variability.

Background: The incidence of spinal metastatic disease has risen with improved cancer survivorship. Separation surgery, the current standard surgical treatment, does not fully address spinal deformity. Advances in operative management warrant reevaluating maximal tumor resection and anterior column reconstruction with corpectomy. Methods: An IRB-approved retrospective single-center review of 63 patients was performed. Demographics, tumor characteristics, clinical and radiographic data, treatments, and neurological and survival outcomes were analyzed. Results: The mean age at presentation was 63.5 ± 9.6 years (range, 37-84 years) and 28 patients (44.4%) were female. Functional outcomes, measured by KPS, RAND-36 survey scores and Oswestry Disability Index all improved postoperatively (pre- vs postop: 70 to 80 (p=0.0056), 26.5 to 46.4 (p=0.0081), and 28.9 to 16.9 (p=0.0613), respectively). Spinal alignment also improved, with Cobb angle measurements showing a reduction in spinal kyphosis from -5 to 0 (p=0.021). Nine patients (14.5%) had non-fatal postoperative complications. The median OS for this cohort was 14.4 months (range, 0.6-145.0 months) with median follow-up time of 15.5 months. Conclusion: In oligometastatic spinal disease patients with good functional status, corpectomy for decompression of neural elements, deformity correction, and spinal stabilization is associated with improvements in pain and functional outcomes without overwhelming morbidity.

This study aimed to develop a high-quality dry emulsion incorporating omega-3, 6, and 9 fatty acid-rich ostrich oil for use as a dietary supplement. Extracted from abdominal adipose tissues using a low-temperature wet rendering method, the ostrich oil exhibited antioxidant properties, favorable physicochemical properties, microbial counts, heavy metal levels, and fatty acid compositions, positioning it as a suitable candidate for an oil-in-water emulsion and subsequent formulation as a dry emulsion. Lecithin was employed as the emulsifier due to its safety and health benefits. The resulting emulsion, comprising 10% w/w lecithin and 10% w/w ostrich oil, was stable, with a droplet size of 3.93 ± 0.11 μm. This liquid emulsion underwent transformation into a dry emulsion to preserve the physicochemical stability of ostrich oil, utilizing Avicel® PH-101 or Aerosil® 200 through a granulation process. Although Aerosil® 200 exhibited superior adsorption, Avicel® PH-101 granules surpassed it in releasing the ostrich oil emulsion. Consequently, Avicel® PH-101 was selected as the preferred adsorbent for formulating the ostrich oil dry emulsion. The dry emulsion, encapsulated with a disintegration time of 3.11 ± 0.14 min for ease of swallowing, maintained microbial loads and heavy metal contents within acceptable limits. Presented as granules containing butylated hydroxytoluene, the dry emulsion showcased robust temperature stability, suggesting the potential incorporation of animal fat into dry emulsions as a promising dietary supplement.

During the postpartum period, psychological disorders may emerge. Aims and objectives: 1 With the current study, we aim to raise awareness among healthcare professionals about postpartum depression (PPD) in women. To reach the aim we will perform the following tasks: (i) identify biological peripartum risk factors and calculate pooled prevalence of PPD for each of them; (ii) explore the strength of relationship between peripartum risk factors and PPD; (iii) rank the predictors by their prevalence and magnitude of association with PPD. The knowledge obtained will support the development and implementation of early diagnostic and preventive strategies. Methods and analysis: we will systematically go through peer-reviewed publications available in the PubMed search engine and online databases: Scopus, Web of Science, EMBASE. The scope of the review will include articles published any time in English, Arabic, or Polish. We will deduplicate literature sources with the Covidence software, evaluate heterogeneity between the study results, and critically assess credibility of selected articles with the Joanna Briggs Institute’s bias evaluation tool. The information to extract is incidence rate, prevalence, and odds ratio between each risk factor and PPD. A comprehensive analysis of the extracted data will allow us to achive the objectives. The study findings will contribute to risk stratification and more effective management of PPD in women.

The vacuolar proton translocating ATPase (V-ATPase) is a transmembrane multi-protein complex fundamental in maintaining a normal intracellular pH. In the tumoral contest, its role is crucial since the metabolism is mainly based on anaerobic glycolytic reactions. Moreover, the neoplastic cells use the V-ATPase to extrude chemotherapy drugs to the extra-cellular compartment, as a drug-resistance mechanism. In glioblastoma (GBM), the most malignant and incurable primary brain tumor, the expression of this pump is upregulated, making it a new possible therapeutic target. In this work, the bafilomycin A1 induced-inhibition of V-ATPase in patients-derived glioma stem cell (GSC) lines was evaluated together with temozolomide, the first-line line therapy against GBM. In contrast with previous published data, the proposed treatment did not overcome the resistance to the standard therapy. In addition, our data showed that nanomolar dosages of bafilomycin A1 lead to the blockage of the autophagy process and cellular necrosis, making the drug unusable in models that are more complex. Nevertheless, the increased expression of V-ATPase following bafilomycin A1 suggests a critical role of the proton pump in GBM stem component, encouraging the search for novel strategies to limit its activity in order to get around the resistance to the conventional therapy.

Despite extensive use of intravitreal anti-vascular endothelial growth factor (anti-VEGF) biologics for over a decade, neovascular age-related macular degeneration (nAMD) or choroidal neovascularization (CNV) continues to be a major cause of irreversible vision loss in developed countries. Many nAMD patients demonstrate persistent disease activity or experience declined responses over time despite anti-VEGF treatment. The underlying mechanisms of anti-VEGF resistance are poorly understood, and no effective treatment strategies are available to date. Here we review evidence from animal models and clinical studies that supports the roles of neovascular remodeling and arteriolar CNV formation in anti-VEGF resistance. Cholesterol dysregulation, inflammation, and ensuing macrophage activation are critically involved in arteriolar CNV formation and anti-VEGF resistance. Combination therapy by neutralizing VEGF and enhancing cholesterol removal from macrophages is a promising strategy to combat anti-VEGF resistance in CNV.

Movement disorders can be associated with various drugs and systemic diseases, posing diagnostic challenges for clinicians. This review explores the spectrum of movement disorders associated with pharmacological agents and medical conditions. Drug-induced movement disorders encompass a broad range of conditions resulting from exposure to medications that affect several neurotransmitters. Neuroleptic medications can lead to tardive dyskinesia, characterized by involuntary, repetitive movements. Antipsychotics and antiemetics, including metoclopramide, may induce acute dystonic reactions. Other drugs, such as dopamine receptor-blocking agents, can contribute to drug-induced parkinsonism. Beyond medications, movement disorders can also arise secondary to systemic diseases. Metabolic disorders like Wilson's disease, characterized by copper accumulation, may manifest as chorea or dystonia. Inflammatory conditions such as rheumatoid arthritis and systemic lupus erythematosus can result in secondary movement disorders due to autoimmune-mediated processes affecting the central nervous system. Movement disorders linked to drugs or systemic diseases often necessitate a thorough clinical evaluation, including detailed medication histories and comprehensive systemic assessments. Neuroimaging, laboratory investigations, and, in some cases, cerebrospinal fluid analyses and electrodiagnostic studies help in establishing accurate diagnoses. Management involves addressing the underlying cause, modifying medications, and employing symptomatic treatments.

Incretin effect helps in regulating glucose homeostasis and maintaining glycaemic control within the human body. This effect is achieved by the two naturally occurring incretin hormones: glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Such hormones released by specialized entero-endocrine cells of the gastrointestinal tract cause insulin augmentation after food consumption. However, incretin effects are impaired in type 2 diabetic, primarily attributed to the deterioration of GLP-1 function along with decreased GLP-1 receptor expression. Targeting this hormone has, therefore, become an important therapeutic approach to treat this diabetic condition. Native GLP-1’s brief half-life and rapid proteolytic degradation have generated significant enthusiasm in uncovering the long-acting GLP-1 receptor (GLP-1R) agonists to manage type 2 diabetes. These synthetic peptides mimic the natural GLP-1 to activate GLP-1R and effectively exert various physiological benefits in terms of weight management, blood pressure, lipid profile, obesity and major adverse cardiovascular event. This review paper provides insights into the structure, function and expression of GLP-1 and its receptor. It also summarizes existing literature regarding different types of GLP-1 receptor agonists, their effects on blood pressure and how they exert their actions. While animal models have contributed significantly to this area of study, the scarcity of human studies is noted, indicating a need for more investigation in this domain. Expanding research in humans will help in comprehending the impact of GLP-1 receptor agonists on blood pressure regulation and their underlying mechanisms.

Caused by pathogenic microorganisms, such as bacteria, parasites, fungi, among others, infectious diseases can spread directly or from one individual to another. According to the World Health Organization, these diseases are known to cause high mortality rates, severe burdens of disability and serious worldwide aftermaths. The inappropriate use of antibiotics in humans are the main origins of the development of drug-resistant pathogens, which reduce the efficacy of these therapies, thus accentuating the need to search for effective antimicrobials. Medicinal plants have served as starting material for the preparation of a number of antimicrobial agents. To this end, the present study highlights the green synthesis of Cocos nucifera-based nanomaterials and evaluation of the mechanistic basis of their antimicrobial action. Accordingly, Cocos nucifera extract was used to reduce different concentrations (5, 10 and 20 mM) of silver nitrate solution to afford silver nanoparticles (AgNPs). These entities were further incorporated onto activated carbons (obtained by chemical activation using sulphuric acid as activation agent) to generate the nanocomposites. The antimicrobial activity of the as-prepared nanomaterials was evaluated using the broth microdilution method, while, the antioxidant activity was assessed through standard methods, such as 2,2-diphenyl-1-picrylhydrazyl (DPPH), and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays. Cytotoxicity of potent nanomaterials was assessed on Vero cells by spectrophotometric method. As a result, nanoparticles were successfully synthesized as evidenced by the color change of the solution from transparent to dark brown. Further characterization was carried out by UV-visible spectroscopy that showed an intense absorption spectrum at 433 nm. Fourier Transform Infrared Spectroscopy (FTIR) revealed the functional group moieties involved as a capping and reducing agent in the synthesis of AgNPs. The incubation of nanomaterials with selected bacterial and fungal strains led to significant inhibitory effects of these pathogens with minimum inhibitory concentrations ranging from 7.813 to 250 μg/ml. In antioxidant assays, the nanocomposites presented scavenging activities comparable to that of ascorbic acid. Cytotoxicity experiment revealed no toxic effects on the human mammalian cells Vero (range of selectivity indices: from &gt;4 to &gt;128). These results provide evidence of the implication of Cocos nucifera-based nanomaterials in targeting bacterial or fungal systems that mediate free-radical damage or by inhibiting the oxidative damage caused by selected bacteria and fungi, the most susceptible being Escherichia coli and Candida albicans, respectively.

The study aims to compare the efficacy and safety of bulking agents and single-incision slings in the treatment of urinary incontinence in 159 patients during a 29-month follow-up period. Of the 159 patients suffering from stress urinary incontinence, 64 were treated with bulking agents and 75 with a single incision sling. The ICIQ-UI-SF, PISQ-12, FSFI, FSDS, and PGI-I were used to assess efficiency and quality of life. In the 29-month follow-up, the bulking agents showed significantly increased efficacy and safety. Compared to the ones treated with a single-incision sling, the patients treated with bulking agents showed less and mild postoperative complications. Furthermore, at our follow-up there was no discernible difference in terms of effectiveness or quality of life between patients treated with bulking agents and those treated with single-incision slings

Background: MRI-guided prostate biopsies from visible tumor-specific lesions (TBx) can be used to diagnose clinically significant carcinomas (csPCa) requiring treatment more selectively than conventional systematic biopsies (SBx). Ex vivo fluorescence confocal microscopy (FCM) is a novel technique that can be used to examine TBx prior to conventional histologic workup. Methods: TBx from 150 patients were examined with FCM on the day of collection. Preliminary findings were reported within 2 hours of collection. The results were statistically compared with the final histology. Results: 27/40 (68%) of the csPCa were already recognized in the intraday FCM in accordance with the results of conventional histology. Even non-significant carcinomas (cisPCa) of the intermediate and high-risk groups (PSA &gt; 10 or 20 ng/ml) according to conventional risk stratifications were reliably detectable. In contrast, small foci of cisPCa were often not detected or were difficult to distinguish from reactive changes. Conclusion: The rapid reporting of preliminary FCM findings helps reduce the psychological stress on patients an can improve the clinical management of csPCa. Additional SBx can be avoided in individual cases, leading to lower rates of complications and scaring in the future surgical area. Additional staging examinations can be arranged without losing time. FCM represents a promising basis for future AI-based diagnostic algorithms.

An association between subtle changes in T2 white matter hyper-intense signals (WMHS) de-tected in fetal brain magnetic resonance imaging (fbMRI) and congenital cytomegalovirus (CMV) infection has been established. The research aim of this study is to compare children with congenital CMV infection with neurodevelopment outcome and hearing deficit with and with-out WMHS in a prospective historic cohort of 58 fbMRIs. Of these, WMHS was detected in 21. The median infection week of the WMHS group was earlier than the normal fbMRI group (8 and 17 weeks of gestation respectively). The proportion of infants treated with valganciclovir in the WMHS group was distinctly higher. Hearing impairment was not significantly different be-tween the groups. VABS scores in all 4 domains were within normal range in both groups. The median score of the motor skills corrected for week of infection was better in the WMHS group. A multivariate analysis using week of infection interaction variable of WMHS and valganciclo-vir treatment showed better motor score outcomes in the valganciclovir treatment group despite earlier week of infection. WMHS was not associated with neurodevelopmental outcome and hearing deficit. In our cohort valganciclovir treatment may have a protective effect on fetuses with WMHS by improving neurodevelopment outcome.

Salmonella enterica serovar Typhi, is one of the major infection spreading from consuming contaminated food and water. The poor sanitation is one the major cause for successful infection. S. typhi is responsible for causing typhoid fever, which is a growing public health concern in developing countries. This bacterium has acquired antimicrobial resistance to many promising which is a growing health concern for community. This study is aim to elucidate the molecular complexity of flouroquinolone resistance in S. Typhi isolates (n=286). Genomic data was downloaded from NCBI and analysis was done by Resfinder, MLST, and Pointfinder. Genomic analysis unveils a complex resistance profile, featuring antimicrobial resistance genes (ARG) including blaCTXM-15, blaTEM-1D, catA1, dfrA7, qnrS1, sul1, sul2, and tetA(B). The investigation focuses on mutations in DNA gyrA, parC, and qnrS1 genes which plays an important role in quinolone resistance. Mutation analysis reveals mutations such as DNA gyrA_S83F, DNA gyrA_D87N, DNA gyrA_S83Y, DNA gyrB_S464F, parC_S80I, and parE_L416F with the presence of qnrS1 gene produces resistance against quinolones. The Docking studies was conducted by “Autodock vina” and visualize by “Discovery studio” which demonstrate that these mutations leads to ciprofloxacin resistance, indicating reduced binding affinity, and altered solvent accessibility which indicates the structural changes at mutation sites. This study provides crucial insights into the molecular mechanisms driving flouroquinolone resistance in S. typhi, guiding future strategies to combat antibiotic resistance. Further validation through experimental mutagenesis is recommended, for targeted therapeutic interventions against the mounting threat of antibiotic-resistant S. typhi.

Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome) is a rare autosomal recessive lysosomal storage disease (LSD) caused by deficiency of a hydrolase enzyme, N-acetylgalactosamine-6-sulfate sulfatase, and characterized clinically by mainly musculoskeletal manifestations. The mechanisms underlying bone involvement in humans are typically explored using invasive techniques such as bone biopsy, which complicates analysis in humans. We compared bone proteomes using DDA and SWATH-MS in wild-type and MPS IVA knockout mice to obtain mechanistic information about the disease. Our findings reveal over 1000 dysregulated proteins in knockout mice, including those implicated in oxidative phosphorylation, oxidative stress (reactive oxygen species), DNA damage, and iron transport, and suggest that lactate dehydrogenase may constitute a useful prognostic and follow-up biomarker. Identifying biomarkers that reflect MPS IVA clinical course, severity, and progression have important implications for disease management.

The present review compared the efficacy of soft tissue substitutes (STS) and autogenous free gingival graft (FGG) or connective tissue graft (CTG) in mucogingival procedures to increase keratinized tissue (KT) width around teeth and implants. Two independent examiners performed the electronic search on Medline and Cochrane Library based on the following PICO’s format: (P) adult patients; (I) soft tissue substitutes and FGG/CTG; (C) STS vs CTG; STS vs FGG; STS vs CTR; (O) KT width gain; (S) Systematic Reviews, Randomized Controlled Trials. Results showed that around teeth, all biomaterials showed superior performance compared to CAF alone for treating gingival recessions. However, when compared to CTG, ADM yields the most similar outcomes to the gold standard (CTG), even though in multiple recessions CTG still continue to be considered the most favorable approach. Use of STSs (acellular matrix or tissue engineered) in combination with an apically positioned flap resulted in a significantly less gain of KTW compared to what achieved with FGG and APF. Around dental implants, free gingival grafts were deemed more effective than soft tissue substitutes in enhancing keratinized mucosa width.

With the breakthroughs and innovative developments in nanotechnology, research on the application of nanomedicine in cancer therapy has so far seen tremendous expansion and success. Intelligent stimulus-responsive nanocarriers are an emerging field of research and have great interest in cancer therapy owing to the fascinating properties such as excellent targeting function, high drug loading capacity, and targeted on-demand release properties. Responsive nanomaterials can be designed and constructed according to the dosing context and therapeutic needs, at the same time, activated by internal bio-stimuli (pH, redox, and enzymes) and/or external stimuli (ultrasound, light, temperature, and magnetic), respectively. What’s more, smart nanocarriers are also utilized for the precise and controllable release of antitumor drugs from cancer tissues and cells to achieve efficient diagnosis and treatment of tumors. Deeply investigated, responsive nanocarriers have attracted considerable attention due to their ability to release precisely at tumor-specific sites. Herein, we review the recent advances of novel stimuli-responsive nanocarriers in the field of cancer therapy. Finally, the challenges and application prospects of smart nanocarriers are further elaborately discussed.

We conducted this systematic review with the objective to understand the efficacy and safety of proton pump inhibitors [PPIs] in the pediatric population. We have used PubMed to identify randomized controlled trials [RCTs] published between 1st June 2010 and 30th June 2023, in patients from birth to 18 years old, with gastroesophageal reflux disease [GERD], who received treatment with any PPI. The literature yielded 76 articles and 13 met inclusion criteria. For infants, PPIs were equal to placebo in reducing GERD symptoms in 4 articles. In 1, the number of GER episodes and esophageal acid exposure were lower in infants who received PPIs and left lateral position, but there was no significant improvement in symptoms. In another publication, the combination of PPIs and feeding modifications [FM] was not more effective than PPIs alone. For children and adolescents, PPIs were effective in improving symptoms and achieving mucosal and histological healing, which was subsequently maintained. To conclude, PPIs are not effective to reduce symptoms related to GERD in infants, but are effective in older children, along with histological remission. Generally, PPIs are well tolerated, but it is important to not forget the possible adverse events [AE], especially if they are used for a long time.

Introduction: Medication overuse headache (MOH) is a secondary headache that occurs 15 or more days per month in patients with preexisting headache. This can result from the excessive (10 or 15 days/month) use of drugs for acute or symptomatic headache therapy. Aim: To examine the relationships between demographic parameters, illnesses and habits of life, clinical type and length of previous headache and MOH and clinical features of MOH. Materials and methods: This study was conducted at the Clinic of Neurology, Clinical Center of Niš, and included 83 patients (11 men and 72 women) who were first diagnosed with MOH. The mean age of the patients in the study cohort was 40.5 ± 11.6 years. The study was performed in strict accordance with the Declaration of Helsinki after informed consent was obtained from each participant in the study. The study was approved by the local ethics committee. Results: In the study cohort, there were more women (86.7%), nonsmokers (59%), those who did not consume alcohol (95.2%), those who were physically inactive (90.4%), those who consumed caffeinated beverages (89.2%), and those with diseases of the cardiovascular (12%) or osseous joint system (10.8%). MOH was most commonly generated by chronic migraine (64%). The duration of MOH until diagnosis was 5.1 ± 5.5 years. The following MOH characteristics were observed: moderate pain (45.8%), bilateral localization (56.6%), temporal presentation (65.1%), and neck tightness (81.9%). Common (41%) and combination analgesics (48.2%) were used most frequently, 15 to 25 days per month. The impact of MOH on daily life was assessed as significant (HIT - 65.4 ± 5.5), correlating with the duration of earlier chronic headaches (r = 0.327, p = 0.003). Conclusion: MOH can be generated by the transformation of a previous chronic headache due to overuse of analgesic therapy. The MOH significantly affects all aspects of a patient's life. MOH can be prevented by educating patients by limiting the use of analgesic therapy, especially in the at-risk group (middle-aged women with chronic migraines).

Abstract: This study explores the antibacterial and antifungal activity of four floral honey types (12 samples) (A. seyal, Zizuphus spina-christi, Cucurbita maxima and A. nilotica) as related to their phenolic content, antioxidant capacity, and assessing their cytotoxic effects. The cup-plate agar diffusion assay was employed to examine the antimicrobial potency against different pathogens including Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Aspergillus niger and Candida albicans. Scavenging activity, total phenolic, flavonoid contents, and cytotoxicity were determined by the DPPH radical scavenging, Folin–Ciocalteu, spectrophotometry, and Brine shrimp lethality, bioassays respectively. All assessed honeys significantly inhibited the growth of the tested pathogens. Both Acacias honey exhibited high antioxidants with IC50: 6.68 and 9.08 mg/ml respectively for A. seyal and A. nilotica. The total phenol content varied from 5.75 to 67.95 mg (GAE)/100 g while the overall flavonoid content varied from 0.15 to 0.5mg (QE)/100 g. All honey types expressed no cytotoxicity effects one cell lines. Thus the study, supports the existing antimicrobial activity of honey. However, the strong antimicrobial activity of Cucurbita and Ziziphus honeys, with their corresponded poor antioxidant furtherly provides evidence that the high levels of phenolic substances in honeys is not always the only cause of their antimicrobial potency.

Background: Crohn’s disease (CD) and ulcerative colitis (UC) are well defined phenotypes of chronic inflammatory bowel diseases (IBD). A mechanism of inflammation in these diseases is partially controlled by intestinal dendritic cell (DC). In this study we observed a mature CD83+DC in colonic bioptic samples, and its correlation with disease phenotype and activity. Methods: There were 219 subjects included in the study: 100 with UC, 44 with CD and 75 healthy subjects. Colonic biopsy specimens were incubated with primary antibody Anti-CD83. Intraepithelial CD83+DC were counted per 100 enterocytes. Presence of CD83+DC was analysed according type of IBD, histopathologic inflammation activity and treatment outcome. Results: The presence of mature CD83+DCs (0, ≥1) significantly differed among disease types of IBD (p=0.001), histologic inflammation activity (p=0.049) and applied therapy (p=0.001). The odds for CD83+DC presence was 5.2 times higher in CD group than in control/UC group. The odds for CD83+DC presence was 2.6 times higher in subjects without inflammation or chronic inflammation than in acute inflammation. It was also 3.7 times higher in subjects without therapy. The cut-off value 0.5 CD83+DC (Rock analysis area=0.699; SE 0,046;p<0.001;95%CI:0.609-0.788) had been assessed as a differentiation marker between UC and CD. Conclusion: Presence of CD83+DC could be used as a possible parameter in distinction between UC and CD, as well as predictor of inflammation activity and treatment outcome.

OBJECTIVE: Cervical cancer is a major cause of cancer-related mortality, necessitating effective screening and diagnostic methods. This study aimed to assess the performance of cervicovaginal smear (CVS) and Human papilloma virus (HPV)-DNA cotest. STUDY DESIGN: The pathology results of 225 female patients who underwent HPV-DNA testing with CVS between 2014 and 2022 and were subsequently diagnosed by colposcopic cervical biopsy or second CVS were retrospectively analyzed. RESULTS: CVS samples showed Atypical Squamous Cells of Undetermined Significance (ASCUS), Low-grade squamous intraepithelial lesion (LSIL), High-grade squamous intraepithelial lesion (HSIL) and cervical cancer. Concordance between the first and second diagnoses demonstrated moderate agreement for LSIL. ASCUS cases exhibited a significant correlation with HPV-DNA positivity and higher-grade cervical lesions. In biopsy, sensitivity and specificity for CIN 2 were 67.8% and 67.9%, respectively, while for CIN 3, they were 81.8% and 58.5%. HPV testing showed significant correlation with histopathologic results. In women over 40 years, more intraepithelial lesions were diagnosed compared to younger women (p<0.005). The conventional smear technique proved reliable in detecting high-grade lesions. CONCLUSION: Despite the limitations of our study, our results emphasize the value of HPV-DNA testing to avoid unnecessary interventions and to establish appropriate follow-up strategies.

Given that evaluating suspected child maltreatment is a challenging task, we aimed to begin to explore how laboratory test results may assist in its detection. Hence, we have examined biomarker differences between 137 children entering out-of-home care and 126 children living in their own homes. Each child entering Majorcan institutionalized care was randomly matched for gender and age with children living in their homes and the same health area. Concerning basic hematological and biochemical values, children placed in out-of-home care differed significantly from children remaining at home in four distinct ways. Children at care entry had significantly higher eosinophil counts than children at home; and also had significantly lower levels of transaminase, thyroid-stimulating hormone, triglycerides and LDL-Cholesterol than children living at home. Oxidative stress linked to anxiety disorders and underweight are common features found in children at entry into the care system. The present study shows a relationship between some underweight or oxidative stress biomarkers and the risk of entry into out-of-home care. Medical diagnoses require physicians to select and assemble relevant data from all available information. Accordingly, we should consider the implementation of laboratory checkups in order to identify the abused from the non-abused child better.

The studies regarding macrophage lncRNAs described in this review can help provide valuable information for developing treatments for various pathological conditions involving macrophages. Over the past century, molecular biology's focus has transitioned from proteins to DNA, and now to RNA. Once considered merely a genetic information carrier, RNA is now recognized as both a vital element in early cellular life and a regulator in complex organisms. Long noncoding RNAs (lncRNAs), which are over 200 bases long but do not code for proteins, play roles in gene expression regulation and signal transduction by inducing epigenetic changes or interacting with various proteins and RNAs. These interactions exhibit a range of functions in various cell types including macrophages. Notably, some macrophage lncRNAs influence the activation of NF-κB, a crucial transcription factor governing immune and inflammatory responses. Macrophage NF-κB is instrumental in the progression of various pathological conditions including sepsis, atherosclerosis, cancer, autoimmune disorders, and hypersensitivity. It orchestrates gene expression related to immune responses, inflammation, cell survival, and proliferation. Consequently, its malfunction is a key contributor to the onset and development of these diseases. This review summarizes the role of lncRNAs that regulate NF-κB in macrophage activation and inflammation, especially focusing on their implications in human diseases and their potential as therapeutic targets

Epidemiological and clinical evidence have extensively documented the role of obesity in the develop-ment of endometrial cancer. However, the effect of fatty acids on cell growth in endometrial cancer has not been widely studied. Here we reported that palmitic acid significantly inhibited cell proliferation of endometrial cancer cells and primary cultures of endometrial cancer, and reduced tumor growth in a transgenic mouse model of endometrial cancer, in parallel with increased cellular stress and apoptosis and decreased cellular adhesion and invasion. Inhibition of cellular stress by N-acetyl-L-cysteine effec-tively reversed the effects of palmitic acid on cell proliferation, apoptosis and invasive capacity in the endometrial cancer cells. Palmitic acid increased the intracellular formation of lipid droplets in a time- and dose-dependent manner. Depletion of lipid droplets by blocking DGAT1 and DGAT2 effectively increased the ability of palmitic acid to inhibit cell proliferation and induce cleaved caspase 3 activity. Collectively, this study provides new insight into the effect of palmitic acid on cell proliferation, inva-sion and the formation of lipid droplets that may have potential clinical relevance in the treatment of obesity-driven endometrial cancer

Injuries to humans caused by wild animals, particularly bears, are rarely mentioned in the literature. The frequency of such injuries is high in Siberia, which is a territory surrounded by dense forests and is a habitat of brown bears. Only for the last 4 months (September - December) 4 episodes of bear attacks on humans were registered in Khakassia, Russia. We present a clinical case of rehabilitating a patient after a bear attack for multiple fragmentary fracture of the facial skeleton with displacement of bone fragments, subcutaneous emphysema of soft tissues of the face, parietal and right occipital regions, and paranasal sinus hemorrhage on the left side. The nature of the injury was enhanced by the trauma to the upper extremity, with which the patient defended himself against the animal. In addition to the damage to the face, the bear tried to open the cranium, which was evidenced by 4 furrows from the canines, 2 on the frontal and 2 on the occipital bones of the skull. The complex treatment of the patient included both maxillofacial and reconstructive surgery, and at the stage of outpatient treatment the formation of normotrophic scars with the help of neodymium laser and injections of heterogeneous composition consisting of micro-particles of "cross-linked" collagen of animal origin, placed in a gel identical to the natural extracellular matrix.

: Cardiac surgery (CS) with extracorporeal circulation (ECC), induces oxidative stress and systemic inflammatory response, which may seriously affect postoperative lung function. We aimed to test if high parenteral (200mg/kg/24h) perioperative (48h) doses of Vitamin C (VitC) may reduce the incidence and severity of postoperative pulmonary complications (PPC) in selected CS patients. Single centered, prospective, randomized, single-blinded, interventional study included 150 patients, assigned to control group A (n=75) and interventional group B (n=75). Group B intraoperatively received 1/4 of the planned daily Vit C dose (200mg/kg/24h), diluted in 10 ml of normal saline, divided into three parts, while Group A received an equal volume of normal saline at the same time frames. After 6 h from the first intraoperative dose, the following regimen was applied: Group B: 200 mg/kg/24h - 30 min i.v. infusion of VitC in 50 ml of normal saline, every 6h, for the next 48h, and Group A: 30 min i.v. infusion of an equal volume of normal saline every 6 hours, for the next 48h. Modified Kroenke’s score was used to determine the incidence and severity of PPC. The overall incidence of PPC was 36.7% and was significantly lower in Group B (13.3% v.s. 60.0%, p&lt;0.001). The severity of PPC was also significantly lower in Group B [1(1) v.s. 3(2), p&lt;0.001]. Besides, patients from Group B had significantly less damaged lungs and better postoperative renal function, shorter ICU stay, fewer ICU re-admissions, and lower hospital mortality. High parenteral daily VitC doses (200mg/kg/24h) given to selected CS patients for 48h after CS are safe and effective in reducing the incidence and severity of PPC. Further multicenter RCT is needed to confirm these results.

Background: Takayasu’s arteritis is a rare type of vasculitis, with severe complications like stroke, ischemic heart disease, pulmonary hypertension, secondary hypertension, aneurysms. Diagnosis is conducted by clinical and angiographic criteria. Treatment is medical and surgical, but unfortunately, the outcome is reserved. Case presentation: A 34- year- old Caucasian women had an ischemic stroke (2009). She was diagnosed with Takayasu’s arteritis and she received treatment with methotrexate, prednisolone, antiplatelet agents, with a mild improvement of clinical state. After 5 years (2014) she associated ascending aorta aneurysm, pulmonary hypertension, mild aortic regurgitation. The surgical treatment solved both ascending aorta aneurysm and left carotid artery stenosis (ultrasound in 2009 and computed tomography angiogram in 2014). Morphopathology revealed typical appearance for Takayasu’s arteritis. Tumor necrosis factor inhibitors (TNF-inhibitors) were associated to methotrexate. At 48 years (2023) she developed coronary heart disease (angina, electrocardiogram); echocardiography revealed severe pulmonary hypertension; angiography described normal coronary arteries, abdominal aorta pseudoaneurysm and arterial-venous fistula, with origin in right coronary artery and drainage on medium pulmonary artery. The patient refused surgical/ interventional treatment; she received again TNF- inhibitors, methotrexate, antiplatelet agents, statins. Conclusions: This case report presents us a severe form of Takayasu’s arteritis. We consider that morphopathology had a great importance in revealing to clinicians the typical appearance and the stadialization of inflammatory arterial process: acute or chronic. The verdict of morphopathologist was chronic phase, with acute relapses, so we decided that immunosuppressive treatment was still necessary.

In dermatological practice, disturbances of the skin microbiome are found in various infectious and inflammatory dermatoses featuring one or more skin lesions with loss of tissue, directly exposing skin layers to microbial invasions. Literature data on the incidence of cutaneous-onset sepsis are, however, scarce. This retrospective observational study assessed hospital admissions for primary skin lesions with vs. without bacterial infections and sepsis during 2020-2022 in the largest emergency hospital in NE Romania. Of 509 patients 441 had infected lesions, 78 had sepsis caused by venous ulcers microbial eczema cellulitis, superinfected bullous dermatoses, erysipelas, erythroderma. Cultured samples revealed S. aureus, P. aeruginosa, E. coli, with K. pneumoniae, S. β-hemolytic associated with sepsis even if rarer. Clinical manifestations included ulcerations, erosions, fissures, excoriations, bullae, vesicles, pruritus, tumefaction, edema, fever, chills, pain, adenopathy, mildly altered mental status. Underlying chronic heart failure, atrial fibrillation, anemia, type-1 diabetes mellitus were comorbidities associated with infection and sepsis. Significant associations and risk factors, including their combined effects, are discussed to draw attention to the need for further research and adequate management to prevent sepsis in adult patients of any age presenting with infected skin lesions (especially cellulitis) and comorbidities (especially type 1 diabetes mellitus and anemia).

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that acts on the pancreas to increase insulin and decrease glucagon secretion. Albuminuria is the pivotal marker for diabetic nephropathy, which is the leading microvascular complication of diabetes mellitus. Most of the previous studies mainly focused on the clinical trials of the therapeutic renal protective effect after administration of GLP-1 receptor agonists (GLP-1 RAs), not prior to administration. Therefore, this study aimed to investigate the association between fasting plasma GLP-1 levels and albuminuria before GLP-1 RA administration. A cross-sectional study was designed to evaluate the association between fasting plasma GLP-1 levels and albuminuria in patients with type 2 diabetes mellitus (T2DM). A total of 68 T2DM participants were analyzed from the data at Wonkwang University Hospital in Iksan, Korea. Logistic regression analysis was performed to evaluate the odds ratio (OR) and 95% confidence interval (CI) of the incidence of albuminuria between the GLP-1 low group (Group L) and the high group (Group H). The OR (95% CI) for the incidence of albuminuria comparing the Group L with the Group H of fasting plasma GLP-1 levels was 3.410 (1.160-10.023), p = 0.026 after adjustment for age, gender, fasting plasma glucose, HbA1c, C-peptide, the use of ACE inhibitors or ARBs, SGLT-2 inhibitors, and DPP-4 inhibitors. As a continuous variable, the OR (95% CI) for the incidence of albuminuria associated with the reduction of each 1 pmol/L in fasting plasma GLP-1 levels was 1.673 (1.173-1.870), p = 0.018, after full adjustment. This study showed the negative association between fasting plasma GLP-1 levels and the incidence of albuminuria in Korean patients with T2DM, before GLP-1 RA administration. This result suggests that endogenous GLP-1 may play a role in attenuating albuminuria.

The aim of this retrospective study was to identify myocardial injury after COVID-19 inflamation and to explore whether myocardial damage could be a possible cause of the persistent symptoms following COVID-19 infection in previously healthy individuals. The study included 139 patients who were enrolled between January-June 2021, mean age 46.7±15.2 years, 68 were men, 71 were women without known cardiac or pulmonary diseases. All patients underwent clinical work up, lab. analyses, cardiac ultrasound, and CMR on 1.5 T scanner using a recommended protocol for morphological and functional assessment before and after contrast media application with multi-parametric sequences. In 39% of patients late gadolinium enhancement (LGE) was found as a sign of myocarditis. Fibrinogen was statistically significantly higher in patients with LGE than in those without LGE, (4.3±0.23 vs 3.2±0.14g/L, p<0.05; respectively), as well as D-dimer (1.8±0.3 vs 0.8±0.1 mg/L FEU). Also troponin was statistically significantly higher in patients with myocardial LGE (13.1±0.4ng/L) compared to those with normal myocardium (4.9±0.3ng/L, p<0.001). We demonstrated chest pain, fatigue and elevated troponin to be independent predictors for LGE. Septal LGE was shown to be predictor for arrhythmias. The use of CMR is a potential risk stratification tool in evaluating outcomes following COVID-19 myocarditis.

Healthcare visits were reduced during COVID-19 pandemic causing the disturbance of the sustainability in NAFLD monitoring. Telemedicine acts to maintain connectivity between patients and healthcare professionals. This review aimed to assess telemedicine helps to monitoring in NAFLD. The database was searched from The PubMedCentral and ScienceDirect from 2020 to 2023. We assessed the Cochrane Risk of Bias (RoB) for randomized controlled trial (RCT) and the Newcastle-Ottawa scale for non-RCTs systematic reviews. Meta-analyses with random-effects model to determine the pooled mean difference (MD) and p-value. There were three RCT and two non-RCT were included (n=239) with 56.9% males and the mean age was 51.3 years. Median intervention lasted 5.5 months. The parameter were body weight (BW), body mass index (BMI), waist circumference, liver function (AST/ALT), lipid profile and HbA1c. Metaanalysis showed telemedicine had a significant effect on improving outcomes for BW (MD -2.81: 95% CI, -4.11, -1.51, P 0.0001) and BMI (MD -1.01: 95% CI, -1.47, -0.55, P 0.0001) compared to standard care, while the AST/ALT were not significantly reduced. Other laboratory parameter were decreased from systematic reviews. Telemedicine through mobile-based applications could be an option for monitoring body weight and BMI in NAFLD patients facing the pandemic.

Breast cancer is the most common cancer in women globally, often necessitating mastectomy and subsequent breast reconstruction. Silicone mammary implants (SMIs) play a pivotal role in breast reconstruction, yet their interaction with the host immune system and microbiome remains poorly understood. This study investigates the impact of SMI surface topography on host antimicrobial responses, wound proteome dynamics, and microbial colonization. Biological samples were col-lected from ten human patients undergoing breast reconstruction with SMIs. Mass spectrometry profiles were analyzed for acute and chronic wound proteomes, revealing a nuanced interplay between topography and antimicrobial respondseproteins. 16S rRNA sequencing assessed mi-crobiome dynamics, unveiling topography-specific variations in microbial composition. Surface topography alterations influenced wound proteome composition. Microbiome analysis revealed heightened diversity around rougher SMIs, emphasizing topography-dependent microbial inva-sion. In vitro experiments confirmed staphylococcal adhesion, growth, and biofilm formation on SMI surfaces, with increased texture correlating positively with bacterial colonization. This comprehensive investigation highlights the intricate interplay between SMI topography, wound proteome dynamics, and microbial transmission. The findings contribute to understanding host-microbe interactions on SMI surfaces, essential for optimizing clinical applications and minimizing complications in breast reconstruction.

This is a retrospective chart review of outcomes of maxillofacial microvascular free flap reconstructions in pediatric and adolescent patients. A single head and neck surgical team performed all the included 136 procedures. Demographic and surgical patient data were recorded. Type of transfer performed in each recipient site and major complications were analyzed. Relevant influencing factors, such as age, gender and etiology of defect were determined using the ANOVA test and χ² test of independence. Results indicate a 90% success rate. No significant relation was found between the incidence of total flap loss and patient age, etiology or graft source. The maxillary reconstructions showed a higher incidence of total flap loss compared to mandibular ones (11 vs. 3 cases). Despite the high success rate, the findings underline the necessity for further research to validate these observations and enhance surgical methods for pediatric and adolescent patients.

Type II pneumocytes are the target of SARS-CoV-2 which alters their redox homeostasis to increase reactive oxygen species (ROS). Melatonin (MT) has antioxidant proprieties and protects mitochondrial function. Here we evaluated whether the treatment with MT compensated for the redox homeostasis alteration in serum from COVID-19 patients. We determined oxidative stress (OS) markers such as carbonyls, glutathione (GSH), total antioxidant capacity (TAC), thiols, nitrites (NO2–), lipid peroxidation (LPO), and thiols groups in serum. We also studied the enzymatic activities of glutathione peroxidase (GPx), -S-transferase (GST), reductase (GR), thioredoxin reductase (TrxR), extracellular superoxide dismutase (ecSOD) and peroxidases. There was a significant increase in LPO and carbonyls (p≤0.03) and a decrease in TAC, NO2–, thiols, GSH, (p&lt;0.001) in COVID-19 patients. The activities of the ecSOD, TrxR, GPx, GST, GR and peroxidases were decreased (p≤ 0.04). The treatment with MT favored the activity of the antioxidant enzymes which contributed to increase TAC and restored the lost redox homeostasis. MT also modulated glucose homeostasis functioning as a glycolytic agent and inhibited the Warburg effect. Thus, MT restores the redox homeostasis which is altered in COVID-19 patients and can be used as adjuvant therapy in the SARS-CoV-2 infection.

Background: Silent MRA has shown promising results in evaluating the stents used for intracranial aneurysm treatment. A deep learning-based algorithm was recently introduced by GE. The purpose of this study was to compare the performance of several MRA techniques in lumen visibility in silicone models with flow diverter stents. Methods: Two Surpass Evolve stents of different sizes were implanted in two silicone tubes. The tubes were placed in separate boxes in straight position and in two different curve configurations and connected to a pulsatile pump to construct a flow loop. Using a GE 3.0T scanner, TOF and silent MRA images were acquired, and deep learning reconstruction was applied to the silent MRA dataset. Intra-luminal signal intensity in the stent (SIin-stent), in the tube outside the stent (SIvessel) and of the background (SIbg) were measured for each scan. Results: The SIin-stent/SIbg and SIin-stent/SIv ratio were higher on silent scans and DL-based reconstructions than on TOF images. The stent tips created severe artefacts on TOF images, which could not be observed on silent scans. Conclusions: Our study demonstrated that the DL algorithm improved the quality of the silent technique in evaluating the flow diverter stent patency.

Background and objective K. pneumoniae appeared to be a significant problem due to its ability to accumulate antibiotic-resistance genes. After 2013, alarming colistin resistance rates among carbapenem-resistant K. pneumoniae have been reported in the Balkans. The study aims to perform an epidemiological, clinical, and genetic analysis of a local outbreak of COLr CR-Kp. Material and methods All carbapenem-resistant and colistin-resistant K. pneumoniae isolates observed among patients in the ICU unit of Military Medical Academy, Sofia from 1 January to 31 October 2023 were included. The results were analyzed according to the EUCAST criteria. All isolates were screened for blaVIM, blaIMP, blaKPC, blaNDM, and blaOXA-48. Genetic similarity was determined using the Dice coefficient as a similarity measure and the unweighted pair group method with arithmetic mean (UPGMA). mgrB genes and plasmid-mediated colistin resistance determinants (mcr-1, mcr-2, mcr-3, mcr-4, mcr-5) were investigated. Results There was a total of 379 MDR-K. pneumoniae isolates, 88% of which were carbapenem-resistant. Of them, there were 9 (2.7%) colistin-resistant isolates in six patients. A time and space cluster for five patients was found. Epidemiology typing showed that two isolates belonged to clone A (pts. 1, 5) and the rest to clone B (pts. 2-4) with 69% similarity. Clone A were coproducers of blaNDM-like and blaOXA-48-like and had mgrB-mediated colistin resistance (40%). Clone B isolates had only blaOXA-48-like and intact mgrB genes. All isolates were negative for mcr-1,-2,-3,-4,-5 genes. Conclusions The study describes a within-hospital spread of two clones of COLr CR-Kp with a 60% mortality rate. Clone A were coproducers of NDM-1 and OXA-48-like enzymes and had mgrB-mediated colistin resistance. Clone B isolates had only OXA-48-like enzymes and intact mgrB genes. No plasmid-mediated was found. The extremely high mortality rate and limited treatment options warrant strict measures to prevent outbreaks.

Late type II endoleak (T2EL) arising from internal iliac artery (IIA) network may occur after endovascular aortic repair (EVAR) of aortoiliac aneurysm and may require embolization if sac enlargement is demonstrated. When direct antegrade access to ipsilateral IIA is not achievable due to previous vessel coverage and/or embolization, access to the nidus can be challenging. We report a case of T2EL originating from IIA network causing iliac sac enlargement in a patient previously treated by EVAR for artoiliac aneurysm with IIA embolization and coverage, in which embolization of the nidus was performed through a percutaneous sheathless access to ip-silateral superior gluteal artery (SGA). A literature review dealing with all cases of percutaneous direct SGA access for retrograde embolization of T2EL arising from IIA after previous EVAR is also reported. The research was conducted on Pubmed database using keywords “superior glu-teal artery access,” “transgluteal embolization” and “retrograde embolization for type II endo-leak”. Related articles and references were screened for suitable articles.

Background and Objectives: The COVID-19 pandemic influenced the management of patients with immune mediated rheumatic and musculoskeletal diseases (imRMDs) in various ways. The goal of our systematic review was to determine the influence of the first period of the COVID-19 pandemic on the management of imRMDs. Materials and Methods: Systematic literature search of PubMed, Cochrane and Embase databases, including studies with adult patients on the influence of the COVID-19 pandemic on management of imRMDs. There were no restrictions regarding to study-design except for systematic reviews and case reports that were excluded as well as articles on the disease outcomes in case of SARS-CoV-2 infection. Two reviewers screened the studies for inclusion, and, in case of disagreement, consensus was reached after discussion. Results: A total of 5969 potentially relevant studies were found, and, after title, abstract and full-text screening, 35 studies were included with data from 182’746 patients and 2018 rheumatologists. Non-availability of drugs, e.g., hydroxychloroquine and tocilizuab, was frequent (16–69% of patients). Further, medication non-adherence was reported among patients with different RMDs and between different drugs in 4–46% of patients. Changes to preexisting medication were reported in up to 33% of patients (e.g. reducing dose of steroids or cessation of biological disease-modifying antirheumatic drugs). Physical in-office consultations and laboratory testing decreased and as a consequence newly implemented remote consultations increased greatly with an increase of up to 80%. Conclusion: The COVID-19 pandemic influenced the management of imRMDs, especially at the beginning. Influences were wide-ranging, affecting availability of pharmacies, adherence to medication or medication changes, doctor visits and laboratory testing. New systems of care were set up, including virtual clinics and video consultations. These new forms of health care delivery should be spread and implemented worldwide to routine clinical practice to be ready for future pandemics.

Daptomycin is one of the last therapeutic resources for multidrug-resistant gram- positive bacteria. Despite its structural similarities with glycopeptides, its mechanisms of action and resistance are different, and in some respects are not completely understood. Mutations in several genes have been associated to daptomycin resistance, especially in mprF, walkR, rpoB and rpoC, but their role and importance remain to be elucidated. We have studied mutations in 11 genes, which have been previously associated to daptomycin non- susceptibility, in 9 daptomycin non-susceptible Staphylococcus aureus clinical isolates (daptomycin MIC: > 1mg/L). Susceptibility to daptomycin, vancomycin, linezolid, oxacillin, telavancin and dalbavancin were studied. walkR, agrA, cls1, cls2, fakA, pnpA, clpP, prs, rpoB, rpoC and mprF were amplified by PCR and sequenced. The sequences were compared with the S. aureus ATCC 25923 complete genome (GenBank gi: 685631213) by using BLAST® software. We did not find any changes in walkR, pnpA, prs and clpP. All isolates excepting isolate 5 showed a high number of significant mutations (between 13 and 25 amino acid changes) in mprF. Most isolates also showed mutations in rpo genes, cls genes and fakA. Daptomycin non-susceptibility in S. aureus clinical isolates seems to be reached through different mutations combinations when compared to S. aureus ATCC 25293. Especially mprF and cls1 showed a very high polymorphism in most isolates. Meanwhile, one isolate, St5, showed only single mutation in mprF (P314T).

Pathogenesis of aortic aneurysm and dissection continues to be under discussion. Extracellular matrix (ECM) remodeling processes in the aortic wall are hypothesized to be involved in the development of the disorders. Therefore, in a histological study, we investigated the expression of metalloproteases 1 and 9 (MMP1 and MMP9) and their inhibitors (TIMP 1 and TIMP 2) in cardiac surgery patients. In parallel, we studied the aortic roots by echocardiography. Clinical reports of 111 patients (30 women and 81 men) who suffered from aortic aneurysms and an aortic dissection were evaluated and studied by transesophageal echocardiography. Seven patients, who had coronary heart disease served as „healthy controls“ All patients were surgically operated in the period from 2007 to 2015. A tissue sample of the aortic biopsies was collected from each patient during surgery. Immunohistochemical staining was performed for MMP1, MMP9 and TIMP1, TIMP2 as well. Vascularization was monitored by an CD 31 antibody. In direct comparison, the expressions are not homogeneous. We found smallest changes in the intima area at all. An increase in MMP 1 and MMP 9 expression was detected in both media and adventitia in case of dissections. TIMP 1 and TIMP 2 distribution increases from the lumen of the vessel outward in the wall layers of the aorta. In case of arteriosclerotic changes, intima had a capillarization, but not in the media. Opposite pattern was found in the dissected aortas. Whereas the intima appears empty, vascularization was found in the media and adventitia layers, as well. There are differences in the vascularization between between the aneurysm and dissection and the different layers as well, respectively. A different remodeling process of the ECM in comparison of the vascular layers must be hypothesized. Reading the patterns of staining and with regard to the known inhibitory effect of MMP9 on ECM remodeling, but especially TIMP 2 on neoangiogenesis, a disturbed nutrition and a dysfunctional vasa vasorum remodeling must be assumed as cause of dissection.

“All diseases originate in the gut.” Hippocrates (400 BC) A healthy gut microbiome via the gut-brain-axis (GBA) elevates heart rate variability (HRV), a general measure of health and well-being. A dysbiotic gut microbiome, low in biodiversity and butyrate producers, triggers altered tryptophan metabolism and release of proinflammatory cytokines, predominantly TNF-α, IL-6, and IL-1β, that also characterize chronic inflammation, oxidative stress, and a multitude of diseases, all exhibiting low HRV. Gut dysbiosis upregulates IFN-γ and with it IDO (indoleamine 2,3 dioxygenase). Tryptophan pivots from serotonin synthesis to that of kynurenine, increasing the kynurenine to tryptophan ratio (KTR). An elevated KTR is positively linked to neurodegenerative and autoimmune diseases and negatively linked to HRV. Elevated IDO activity is not only enzymatic but also an intracellular signal transducer potentiated by TGF-β. This cytokine is the primary determinant of the TME. The triple play of a prebiotic (d-mannose), probiotic (bifidobacteria and lactobacilli), and postbiotic (butyrate) might improve intestinal barrier integrity, suppress the inflammatory cytokine triad, balance IFN-γ and TGF-β, depress KTR, elevate HRV, and extend lifespan.

Brimonidine, a selective alpha-2 adrenergic agonist, used for treatment of open-angle glaucoma, has been shown to cause neurological side effects such as unresponsiveness, lethargy, hypoventilation, and stupor, mimicking opioid toxicity. We report one case of transient encephalopathy in a toddler, in whom brimonidine accidental toxicity was sus-pected and then confirmed by a toxicology study. The 8-month-old healthy girl child was taken to the pediatric ER since she was drowsy and hypotonic, with miosis. Brain CT scan and toxicological work-up on blood and urine were negative. Starting from hour +4, the child progressively improved, and by hour +6, she recovered to a normal state of consciousness. A survey of available drugs at the child’s reach showed the presence of brimonidine. Thus, ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was applied to quantify brimonidine in urine and plasma samples, showing 8.40 ng/mL level and 0.79 ng/mL, respectively. To our knowledge, this is the first report for determining brimonidine levels in urine and plasma by UPLC-MS/MS. Insufficient knowledge of the family members about the potential hazards of an apparently innocuous, topical medication such as eye drops may put children at a greater risk of poisoning. Necessary warnings should be better given to parents when prescribing this medication.

Nerve-sparing vs. non nerve sparing surgery (NSS vs. non-NSS) is associated with improved functional outcomes in prostatectomy patients. The aim of the present study is to compare the oncological outcomes of patients with high-risk localized prostate cancer undergoing nerve-sparing and non nerve-sparing robot-assisted radical prostatectomy (RARP). Between November 2002 and December 2018, we prospectively recorded data of patients undergoing RARP for high-risk localized prostate cancer (PCa). NSS (nerve-sparing surgery) was offered based on preoperative clinical characteristics of patients and intraoperative assessment. Patients were stratified into 2 groups according to NSS. The primary outcome was biochemical recurrence (BCR), while positive surgical margin (PSM) and cancer-specific survival (CSS) were secondary outcomes. Logistic regression was used to investigate predictive factors. A total of 779 patients were included in the study, 429 (55.1%) underwent NSS while 350 (44.9%) underwent a non-NSS. After a mean (±SD) follow-up of 192 (±14) months, 328 (42.1%) patients developed BCR, no significant difference was found between NSS and non-NSS group (156 vs. 172; p=0.09). Both univariable and multivariable analysis found that nerve-sparing approach was not a predictor of BCR (p>0.05). NSS vs. non-NSS was not associated with worse oncological outcomes in patients with high-risk PCa

Although a disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS13) serve as the cleaving protease of vWF-multimers, its role in liver ischemia-reperfusion injury (IRI), as well as partial liver transplantation (pLT), remains unknown. First, ADAMTS13 deficient mice were subjected to IRI to investigate the impact on hepatic IRI. Hepatic IRI significantly decreased serum ADAMTS13 activity, while simultaneously up-regulated intrahepatic vWF expression. Ablation of ADAMTS13 aggravated liver IRI by promoting platelet aggregation and disturbing microcirculation in the liv-er accompanied by exacerbated transaminase release and enhanced pro-inflammatory cytokine/chemokines levels. Adjunctive supplementation of recombinant ADAMTS13 (rADAMTS13) improved hepatic microcirculatory failure observed in ADAMTS13-null mice. Immunohistochemistry revealed massive platelet aggregation within hepatic micro-vasculatures in ADAMTS13-null mice, which was attenuated by rADAMTS13 treatment. Consequently, peripheral platelet counts, transaminase release, and pro-inflammatory cytokines/chemokines levels deteriorated in ADAMTS13-null mice, while ameliorated by rADAMTS13 administration. Notably, rADAMTS13 improved IRI-induced pathologies even in WT mice compared with those without. Next, we tested rADAMTS13 in the rat pLT model. Similarly, in rat pLT, ADAMTS13 supplementation attenuated the aforementioned pathologies observed in the experimental mouse model. In conclusion, ADAMTS13 plays a pivotal role in alleviating both hepatic microcirculation and inflammatory responses, thus providing a novel therapeutic approach against LT-related stress.

The practical problem-solving of incidental unreliability of intraoperative neuromonitoring may be the simultaneous neurophysiological recording and the inspection of the surgical field through the camera (the "Real-time neuromonitoring" concept). This would allow the immediate warning of the surgeon on the possibility of the spinal structures insult during but not after the application of the standard procedures in scoliosis surgery (the “Interactive verbal surgeon-neurophysiologist neuromonitoring" concept). This study aimed to compare the advantages, utility, reliability, and time-consuming of both intraoperative neuromonitoring scenarios using non-invasive and innovative recordings from peroneal nerves (PER) versus tibialis anterior muscles (TA) with surface electrodes of motor evoked potentials (MEP) bilaterally as a result of transcranial magnetic (TMS) or electrical (TES) stimulations. Studies were performed in two similar groups ("Real-time neuromonitoring", N=60 and "Interactive verbal sur-geon-neurophysiologist neuromonitoring", N=60) of patients treated surgically because of mainly Lenke 2 type idiopathic scoliosis (IS) pre- (T0), intra- (T1 – before surgical procedures, T2 – after surgical procedures) and postoperatively (T3) as well as in healthy volunteers (N=60, Control). The cumulative parameters of MEP amplitudes and latencies recorded from PER compared to those recorded from TA in healthy volunteers were approximately 67% (1100µV) lower at p=0.007 and 10.6% shorter (3.1 ms) at p=0.04, respectively. A similar trend was also observed in patients from both groups at each follow-up stage. MEP recordings from TA and PER in patients of both groups differed similarly in T0-T3 compared to controls at p=0.008-0.04. MEP parameters in all patients induced by TMS (T0) and TES (T1) did not differ. The parameters of MEP amplitudes recorded from TA and PER intraoperatively in T1 and T2 differed at p=0.04-0.03, indicating the bilateral improvement of neural spinal conduction due to the surgical intervention. Parameters of TMS-induced MEP amplitudes in T3 further increased bilaterally compared to the tests recorded in T0 at p=0.03-0.02. In both groups of patients, an average 51,8 BIS level of anaesthesia minimally affects the variability of the MEP amplitude, especially in PER recordings when ap-plied TES strength was at 98.2 mA. The number of MEP parameter fluctuations, mainly the amplitudes decreasing, was strictly associated with the neurophysiologist's warnings due to transpedicular screws implantation, corrective rods implantation, distraction, derotation, and compression procedures, respectively; at p=0.04-0.03 more in patients from the “Interactive S-N neuromonitoring” group. The average duration of the surgery was significantly shorter (p=0.04) by about 1 hour in the "Real-time neuromonitoring" group. The number of two-way communications between the surgeon and neurophysiologist and vice versa in the "Real-time neuromonitoring" group was reduced by approximately half at p=0.008. The study's results prove the advantages of using the "Real-time neuromonitoring" procedure in increasing safety and non-invasiveness, shortening the time, and lowering the costs of surgical treatment of patients with pathological lateral curvature of the spine. The modifications of the MEP nerve conduction recording technology with surface electrodes from nerves presented in this study enable precise and reliable information on the patient's neurological condition at every stage of applied surgical procedures, even in conditions of slight fluctuations in the anaesthesia.

Until recently there was a paucity of published information on the demographics of themedical and surgical workforce for the subspecialty of liver transplantation. This is relevant as it relates to whether gender equity is being achieved across the workforce. This manuscript focuses on what eventually led to the recognition that more data were required along with what is now actually known. This involves exploring the genders of the liver transplant workforce along with their related academic activities. Potential solutions to address any ongoing imbalances are also examined. The extent and range of gender disparities previously reported for other cohorts of physicians and surgeons, are also apparent amongst the liver transplant workforce in most regions of the world. This also pertains to the higher leadership positions within liver transplant centers as well as for the relevant editorial and scientific congress roles. Common themes/recommendations are now emerging as to how best to address the lack of progress towards gender equity. These include the development and implementation of policies, the removal of barriers to career progression, plus adequate governance. Hence ongoing actions are going to be required to achieve gender equity across the relevant workforce in liver transplantation around the world.

The global increase in obesity has significant health implications, with an increased BMI as a known risk factor for diseases such as type 2 diabetes, cardiovascular diseases, or different cancer types. Long-term effectiveness of diet therapy in addressing morbid obesity is extremely limited with no adequate pharmaceutical agents available as treatment option resulting in bariatric surgery as being the only viable option to achieve and maintain significant long-term weight loss. One important role in the overall human health plays the gut microbiome and its complex composition, which is usually altered and reduced in complexity/diversity in severely obese patients. In this study, the influence of bariatric surgery and the resulting weight-loss on the gut microbiome composition of twelve morbid obese (BMI ≥ 40) female adult central European patients was investigated by comparing the relative abundances of the major microbial phyla Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria prior- and post-surgery. We also aimed to give insight into the major changes of individual prominent and promising future probiotic bacteria characterized by an overall increase in abundance accompanied by a switch of enterotypes. Identifying specific microbial alterations associated with successful weight-loss outcomes may contribute to the development of future therapeutic interventions by supplementation with next-generation probiotics.

Evaluation of the patients after the surgical correction of idiopathic scoliosis in long-term follow-up with the clinical neurophysiology methods has not been presented in detail. This study aimed to compare the results of the neurophysiological studies in 45 girls with scoliosis of Lenke 1-3 types performed pre- (T0), postoperatively (T1, one week after surgery), and 6 months after the surgery (T2). Parameters of surface electromyography during the attempt of maximal contraction (mcsEMG) and transcranially evoked motor evoked potentials (MEP) recorded from anterior tibial muscles, as well as the electroneurography (ENG) of peripheral transmission in the peroneal nerve motor fibers were compared. The results indicate that efferent neural conduction function both centrally and peripherally as well as TA muscle function improve immediately after surgical correction of scoliosis (at p=0.05) and further normalization appears after six months in long-term follow-up (at p=0.03). It has been found in sEMG recordings, that the TA muscle motor unit recruitment function after half a year from surgical treatment in IS patients is comparable to the normal condition. ENG recordings results indicated the gradual retreat of the motor fibers injury symptoms mainly of the axonal type in peroneal nerves, the surgeries improved also the lumbar ventral roots’ neural transmission to the functional status considered as normal. MEP amplitude parameters recorded after the surgical scoliosis correction in T1 indicated a slight improvement in the efferent transmission of neural impulses within the fibers of the spinal tracts; in long-lasting T2 observation, they reached values comparable to those recorded in healthy volunteers bilaterally. Preoperatively (T0) the results of all neurophysiological study parameters in IS patients were asymmetrical at p=0.036-0.05 and recorded as worse on the concave side, suggesting the lateralization of neurological motor deficits. One week postoperatively (T1), this asymmetry was recorded as gradually reduced, showing almost no difference between the right and left sides six months later (T2). The presented algorithm of the diagnostic proceeding pre-, early post-, and long-lasting postoperatively using mcsEMG, MEP, and ENG neurophysiological examinations can be significant not only in making the final decision regarding surgical treatment and its personalization but also helps in precise ascertaining its effects as well as in predicting the final result of IS treatment.

The high prevalence of thyroid nodules and increased availability of neck ultrasound have led to an increased incidence of diagnostic thyroid fine needle aspirations, with approximately 20% yielding indeterminate results. The recent availability of molecular tests has helped guide the clinical management of these cases. This paper aims to review and compare three main commercially available molecular cytology platforms in the U.S. – Afirma GSC, Thyroseq GC, and ThyGeNEXT+ThyraMIR. Sequential improvements of the Afirma GSC and Thyroseq GC tests have led to higher positive and negative predictive values, sensitivity, and specificity. Comparative studies revealed similar diagnostic performance between these tests, with considerations for factors such as cost and processing time. Thyroseq GC provides detailed genomic information and specific management recommendations. ThyGeNEXT+ThyraMIR, though less studied, presents promising results, particularly in miRNA analysis for weak driver mutations. Challenges in interpreting results include variations in reporting and the evolving nature of testing platforms. Questions persist regarding cost-effectiveness and the utility of ultrasound characteristics in selecting candidates for molecular testing. While molecular testing has primarily served diagnostic purposes, advancements in understanding genetic alterations now offer therapeutic implications. FDA-approved options target specific genetic alterations, signaling a promising future for tailored treatments.

In May of 2022, millions of U.S. parents faced uncertainty in safely feeding their infants due to the infant formula shortage. Methods: An anonymous, electronic, cross-sectional, retrospective survey was used. Results: U.S. parents (n =187) whose infants were 10.2 weeks old during the short-age completed the survey. Eighty-one percent of parents switched formulas during the shortage, 87% switched because they could not find the formula they typically used, 34% switched 3-5 times, 29% of parents visited ≥ 4 stores/24 hours and 26% of parents traveled >20 miles/24 hours to purchase formula. Use of infant formula increased (p< 0.01); in infants requiring specialty for-mula, use of intact cow’s milk formula increased (p < 0.05) and use of premature infant formulas decreased (p < 0.05). Infants relying on specialty formulas experienced at least one undesirable outcome compared with non-specialty users. Parents used social media, relatives/friends, and healthcare providers for support during the shortage, but their helpfulness scores were suboptimal. Parents reported needs for greater infant formula availability, free prenatal lactation education and postpartum lactation support. Conclusions: Government, regulatory and healthcare policy oversight are needed to protect the infant feeding system, including more commercially available products, access to banked donor milk and lactation support.

Background: Infantile hemangiomas (IHs) are the most common benign vascular tumors of infancy. Methods: We report our experience of 248 patients with head and neck IHs. Results: The median age on admission was 4 months, and female/male ratio was 2.17. Among the cases, 45% were followed without treatment. No local complications were observed in any of these patients. Propranolol was given to all patients who received medical treatment. The median duration of treatment was 12 months (1-30 months), and the median follow-up period of all patients was 14 months (0-118 months). The treatment response was 98%. Complication rate was 17% and children aged between 3 and 9 months accounted for 60% of patients who developed complications. Most of the complications were local complications such as bleeding, ulcer, and infection. Conclusion: Although most of them regress spontaneously, complications may occur. Propranolol alone is an effective treatment option, and early treatment initiation increases success rates.

The flavonoid silymarin (SMN) has been widely used in preclinical and clinical studies to treat various types of cancer, either alone or in combination with chemotherapy agents. Herein, we investigated the therapeutic efficacy of SMN and its combination with capecitabine (CAP) and irinotecan (IRI) in a mouse model of colon cancer. A modified diet supplemented with SMN (2500 ppm) with mono- and combined therapy of CAP and IRI were used following 1, 2 dimethylhydrazine (DMH)-induced colon cancer. The lipid profile, liver function tests, and cytokine levels were measured. Additionally, the lipid peroxidation and inflammation indices as well as the antioxidant activities were examined. Eventually, western blotting analysis for colonic BAX and Bcl-2 levels and histopathological examination of colon sections were carried out. SMN alone and in combination with the chemotherapeutic agents could attenuate the DMH-induced hyperlipidemia and elevated liver function enzyme levels. SMN supplementation with chemotherapy agents could also improve antioxidant activity and reverse the elevated levels of lipid peroxidation and inflammatory markers. Furthermore, significant upregulation of BAX and downregulation of Bcl-2 were observed. Besides, carcinogen-induced polyp multiplicity, dysplastic, and inflammatory changes were ameliorated considerably by treatment regimens. Our results showed that the potential anticancer properties of SMN could enhance the therapeutic effects of chemotherapy agents and reduce hepatotoxicity.

The relationship between tissue effects, intensity (I), and voltage (V) of a high-frequency alternative current seems well known. However, the translation of the settings of the electrosurgical unit and their use during surgery seems not to be unanimously understood by all surgeons. This results in many variations of surgical technique and plenty of specific questions asked during live surgery. Above 200 V, the heat of the sparks results in the explosion of superficial cells and a cutting effect. With higher voltages, the associated coagulation is increasing. Voltage and amount of energy (Watt=I*V) are independent since a similar amount of energy can be obtained with a continuous current or an intermittent current half the time and a double voltage. Below 200 V, tissue is heated until the steam from boiling tissue stops the current. Therefore, slower heating with less energy or a larger contact area permits deeper coagulation. The maximal output (W) of the electrosurgical unit results in versatility of use besides being a safety measure. The current intensity increases with the area of contact. Therefore, when I*V exceeds the preset output, V has to drop. A limited maximal output thus permits using the same instrument for non-contact cutting with >200V and sparks and coagulation when the contact area is much larger. In conclusion, the tissue effects of electrosurgery vary with the device’s voltage setting (often indicated as force) and the maximal output. The sur-geon’s choice to cut or coagulate by changing the contact area adds versatility.

To date, various chimeric lysins have been developed as efficacious antibiotics against multidrug-resistant bacteria, but direct comparisons of their antibacterial activities have been difficult due to the preparation of multiple recombinant chimeric lysins. Previously, we reported an E. coli cell-free expression method to screen better chimeric lysins against Staphylococcus aureus, but we still needed to increase the amounts of expressed proteins enough to be able to detect them non-isotopically for quantity comparisons. In this study, we improved the previous cell-free expression system by adding a previously reported artificial T7 terminator and reversing the different nucleotides between the T7 promoter and start codon to those of the T7 phage. The new method increased the expressed amount of chimeric lysins enough for us to detect them using Western blotting. Therefore, the qualitative comparison of activity between different chimeric lysins has become possible via the adjustment of the amount variables between samples without protein purification. We applied it to select more active chimeric lysins derived from our previously reported chimeric lysin (ALS2). Finally, we compared the antibacterial activities of our selected chimeric lysins with reported chimeric lysins (ClyC and ClyO) and lysostaphin, and determined the rank orders of antibacterial activities on different S. aureus strains in our experimental conditions.

Background: Evaluation of left ventricular(LV) functions in patients with idiopathic premature ventricular contraction(PVC) with preserved LV Ejection Fraction(LVEF), especially in the subclinical stage, may be of great importance in terms of directing early treatment. Methods: A total of 122 patients, retrospectively recruited, were divided into three groups according to PVC burden: Group 1; 5%PVC<10%, Group 2; 10%PVC<15%, and Group 3; 15% PVC. Transthoracic echocardiography(TTE) was performed to evaluate LV parameters. Results: LV-GLS was found to be significantly lower in groups 2 and 3 with high PVC burden (18.89 ± 1.4, 17.55 ± 2.1, 16.26 ± 1.3; p<0.001 respectively). Correlation analysis revealed a positive and significant correlation between PVC burden with deterioration in LV-GLS (r:0.536; p<0.001). In addition, PVC burden was found to be an independent predictor of LV-GLS deterioration in multiple linear regression analysis(:0.525, p<0.001). The ROC curve analysis demonstrated that a PVC burden cut-off value of 8.4% was associated with a LV-GLS deterioration greater than -18, with a specificity of 75.4% and a sensitivity of 75.4% (AUC: 0.81 [0.73-0.88] 95% CI; p<0.001). Conclusions: PVC burden was an independent predictor of deterioration in LV-GLS. In the presence of subclinical LV injury associated with PVC burden, early catheter ablation strategies may be therapeutically beneficial.

Intellectual disability with speech delay and behavioural abnormalities as well as hypotonia, seizures, feeding difficulties and cra-niofacial dysmorphism are the main symptoms associated with pathogenic variants of ZMYND11 gene. The range of clinical mani-festations of ZMYND phenotype is constantly being expanded by new cases described in the literature. Here, we present 2 previ-ously unreported paediatric patients with neurodevelopmental features diagnosed with missense variants in ZMYND11 gene. It should be noted that one of the individuals manifested with hyperinsulinemic hypoglycaemia (HH), a symptom that was not de-scribed before in published works. Although the reason for the occurrence of HH in our proband is not clear, it is likely that it broadens the spectrum of symptoms characteristic of ZMYND11 syndrome. Thus, this paper contributes to extending the range of possible manifestations of ZMYND disease and further supports its association with neurodevelopmental challenges.

Pachychoroid neovasculopathy (PNV) is a pachychoroid-spectrum disease. As blood circulation throughout the choroid may be involved in PNV pathogenesis, analysis using ultra-wide-field (UWF) fundus imaging is crucial. We evaluated choroidal thickness after half-fluence photodynamic therapy (PDT) combined with intravitreal aflibercept injection for PNV using UWF swept-source optical coherence tomography. Seventeen eyes with PNV that underwent half-fluence PDT with adjuvant single intravitreal aflibercept injection were analyzed. To compare choroidal thicknesses in the central and peripheral choroids, we set subfields <3, <9, and 9–18 mm from the fovea. The <9- and 9–18-mm subfields were divided into four quadrants. Choroidal thickness in each subfield decreased significantly after half-fluence PDT (P<0.001); this reduction was more pronounced in the central area. We also investigated the relationship between the dominant side of the deep choroidal veins that harbor choroidal vein efflux from the macula. When choroidal thickness in the supratemporal and infratemporal 9x9-mm subfields were evaluated, the ratio of choroidal thickness reduction was not significantly different between the dominant and non-dominant sides. The dominant side was not associated with the extent of choroidal thickness reduction in PNV. In conclusion, half-fluence PDT caused thinning of the entire choroid, especially in the central area, in PNV.

The co-occurrence of substance use disorders (SUDs) and psychiatric conditions, often referred to as comorbidity or concurrent disorders, presents intricate challenges in both diagnosis and treatment. This comprehensive narrative review aims to synthesize and critically evaluate the existing evi-dence surrounding the management of individuals with comorbid SUDs and psychiatric disorders. Comorbidity in these domains carries profound implications for clinical practice, research, and policymaking, emphasizing the need for a holistic understanding of the intricate dynamics that arise when these conditions coexist. This review explores recent research findings, evidence-based guidelines, and emerging trends within the field, offering valuable insights for clinicians, re-searchers, and policymakers seeking to navigate the complex terrain of comorbidity in substance use and psychiatric disorders.

Atrial fibrillation (AF), a complex cardiac arrhythmia, necessitates a shift in management paradigms, emphasizing an integrative approach that incorporates lifestyle modifications. Investigations into the role of interleukins and inflammatory mediators are underway, exploring their potential as diagnostic markers and predictors of cardiovascular events in AF. Despite the identification of biomarkers related to cardiac remodeling, their predictive ability for post-cardioversion outcomes remains controversial. Computational models are being developed to understand proarrhythmic contributions and identify anti-AF targets. Addressing the rising global incidence of AF, linked to stroke and heart failure, presents a critical health challenge. As risk factors like obesity prevail, AF becomes a pervasive public health concern, expected to double in prevalence over the next 50 years. The impact on mortality and morbidity, especially through hospitalizations, underscores the need for early detection and effective clinical management. Identifying individuals at increased AF risk becomes crucial for screening and prevention strategies. Lifestyle modifications, including weight management and physical activity, emerge as influential factors in AF management, offering the potential to alleviate symptoms and modify disease progression. The paper concludes by emphasizing the need for safer antiarrhythmic therapies based on AF mechanisms, promising improvement in global AF management. The multifaceted nature of AF etiology requires a broader perspective beyond traditional medical interventions, acknowledging the importance of integrated care to address this significant public health challenge.

The purpose of this study was to evaluate the morpho-functional change of the patellar ligament in dogs affected by cranial cruciate ligament rupture. The hypothesis is that it may show increased thickening and stiffness with increasing days from trauma to diagnosis. Understanding this aspect have implications on the choice of timing to treat patients suffering from cranial cruciate ligament rupture, and also in the contextualization of patellar ligament desmitis pictures after surgical treatment with tibial plateau levelling osteotomy or tibial tuberosity advanced. Thirty-three dogs were affected affected by unilateral cranial cruciate rupture were examined and divided into three groups based on the time elapsed from the onset of lameness to diagnosis: Group 1 (from 1 to 15 days), Group 2 (from 16 to 60 days), Group 3 (over 60 days). Conventional B-mode ultrasonographic and elastosonographic examinations of patellar ligament were performed without sedation for each dog. At the ultrasonographic examination, all dogs showed alterations in the echostructure of the patellar ligament. In addition, the patellar ligament tended to become harder and less soft with increasing days after rupture, although there were not significant differences between groups. Our results showed that as time increases between the onset of cranial cruciate ligament rupture and diagnosis and treatment, the patellar ligament progressively thickens and loses its elasticity.

Endocrine-disrupting chemicals (EDCs) may impact the development of Prostate Cancer (PCa) by altering the steroid metabolism. Although their exact mechanism of action in controlling tumor growth is not known, EDCs may inhibit steroidogenic enzymes such as CYP17A1 or CYP19A1 involved in the production of androgens or estrogens. High levels of circulating androgens are linked to PCa in men and Polycystic Ovary Syndrome (PCOS) in women. Essential Oils or their metabolites like lavender oil and tea tree oil have been reported to act as potential EDCs and contribute towards sex steroid imbalance in case of prepubertal gynecomastia in boys and premature thelarche in girls due to the exposure to lavender-based fragrances. We screened a range of EO components to determine their effects on CYP17A1 and CYP19A1. Computational docking was performed to predict the binding of Essential oils with CYP17A1 and CYP19A1, and functional assays were done using the radiolabeled substrates or Liquid Chromatography high‑resolution Mass Spectrometry and cell viability assays were carried out in LNCaP cells. Many of the tested compounds bind close to the active site of CYP17A1, and (+)-Cedrol had the best binding with CYP17A1 and CYP19A1. Eucalyptol, Dihydro-β-Ionone & (-)-α-pinene showed 20% to 40% inhibition of dehydroepiandrosterone production; and some compounds also effected CYP19A1. Extensive use of these Essential oils in various beauty and hygiene products is common, but only a limited knowledge about their potential detrimental side effects exists. Our results suggest that prolonged exposure to some of these essential oils may result in steroid imbalances. On the other hand, due to their effect on lowering androgen output, ability to bind at the active site of steroidogenic cytochrome P450s, these compounds may provide design ideas for the novel compounds against hyperandrogenic disorders such as PCa and PCOS.

This study investigated the impact of seven-strain probiotic supplementation on the frequency of T helper 17 (Th17) cells, regulatory T (T-reg) cells, Treg/Th17 ratio, and their gene expression in individuals with severe traumatic brain injury (STBI). Probiotics can influence the gut microbiota, modulate the immune response, and prevent or alleviate certain immune diseases. However, it is necessary to clarify whether probiotics can effectively impact Th cells in STBI patient. Despite the great attention to improving the immune system in most diseases, there is currently no accurate mechanism for the use of probiotics in diseases with damage to the head injury, which can be a basis for the use of probiotics. The primary objective of this study is to address this research gap. The present study was a randomized, double-blind, placebo-controlled trial that enrolled 48 STBI patients. They were treated with probiotics or placebo: 4 capsule/day for 14 days. The pre- and post-study evaluation included examining the frequency of Treg, Th17 cells, as well as the expression of associated immunological parameters (Foxp3 and RORγt) and Treg/Th17 ratio in both groups. No significant differences were found between the two groups in terms of subject characteristics (P>0.05). GCS scores at 14 days were significantly higher in the probiotic compared to the placebo group. The probiotic group showed a significant decrease in Th17 cell and RORγt gene expression (P = 0.022 and P< 0.001, respectively), a notable increase in T-reg and FoxP3 gene expression (P= 0.025 and P< 0.001, respectively), and a higher Treg/Th17 ratio compared to the placebo group. Our study provides promising evidence of the beneficial effects of seven-strain probiotic supplementation on Th cells in individuals with STBI.

Obesity is a worldwide epidemic; hence it is crucial to understand how it can be effectively prevented/treated. Thus, obesity should be tackled considering that it is a multifactorial condition. This work examines a wide range of factors and attempts to understand which contribute most to variability in overweight/obesity. Eighty-four subjects with overweight/obesity were recruited. Dietary baseline information was obtained by analyzing three 24-hour recalls. Resting metabolic rate was measured using indirect calorimetry, physical activity through accelerometry, cardiometabolic parameters were determined in blood samples and body composition by anthropometry and bioimpedance. Factor analysis of principal components (PCA) was carried out (SPSS v22.0). Large interindividual variability was observed in dietetic, biochemical, and physical activity measurements (coefficient of variation ≥30%), but body composition was homogeneous. Volunteers had an unbalanced diet and low physical activity. PCA reduced the 26 analyzed variables into 7 factors, accounting for 81,5% of total data variability. The main factor was the ‘‘caloric and lipid factor’’ related to diet, responsible for 25.9% of total variability, followed by ‘‘adiposity factor’’ (16,9%) and ‘‘cardiometabolic risk factor’’ (13,2%). Diet seems to be the factor that contributes the most to data variability in people with overweight/obesity, especially the intake of lipids, energy and proteins.

The fusion of penetrating peptides (PPs), e.g., cell penetration peptides (CPPs), or antimicrobial peptides (AMPs) together with antimicrobial agents is an expanding research field. Specific AMPs, such as lactoferricin B (LfcinB), have demonstrated strong antibacterial, antifungal, and antiparasitic activity, as well as valuable anticancer activity, proving beneficial in the development of anticancer conjugates. The resulting conjugates offer potential dual functionality, acting as both an anticancer and an antimicrobial agent. This is especially necessary in cancer treatment where microbial infections pose a critical risk. Leukemic cells frequently exhibit altered outer lipid membranes compared to healthy cells, making them more sensitive to compounds that interfere with their membrane. In this communication, we revisited and reanalyzed our earlier research on LfcinB and its conjugates. Furthermore, we carried out new experiments with a specific focus on cell proliferation, changes in membrane asymmetric phosphatidylserine location, intracellular reactive oxygen species (ROS) generation, mitochondrial functions, and in vitro bacterial topoisomerase inhibition.

Biofilm-associated bacterial infections are the major reason for treatment failure in many diseases including burn trauma infections. Uncontrolled inflammation induced by bacteria leads to materiality, tissue damage and chronic diseases. Specialized proresolving mediators (SPMs), including maresin-like lipid mediators (MarLs), are enzymatically biosynthesized from omega-3 essential long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA) by macrophages and other leukocytes. SPMs exhibit strong inflammation-resolving activities, especially inflammation provoked by bacterial infection. In this study, we explored the potential direct inhibitory activities of three MarLs on gram-positive (Staphylococcus aureus) and gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacteria in their biofilms that are leading bacteria in burn trauma related infections. We also examined the effects of MarLs on the bactericidal activities of a typical broad-spectrum antibiotics carbenicillin on these bacteria in their preformed biofilms. The results revealed that MarLs combined with carbenicillin can inhibit the survival of gram-positive and gram-negative bacteria in their biofilms although MarLs alone did not exhibit bactericidal activity. Thus, our findings suggest that the combination of MarLs and carbenicillin can lower the antibiotic requirements to kill the bacteria in preformed biofilms.

Introduction: Within primary ARDS, SARS-CoV-2-associated ARDS (C-ARDS) emerged in late 2019, reaching its peak during the subsequent two years. Recent efforts in ARDS research have concentrated on phenotyping this heterogeneous syndrome to enhance comprehension of its pathophysiology. Methods and Results: A retrospective study was conducted on C-ARDS patients from April 2020 to February 2021, encompassing 110 participants with a mean age of 63.2±11.92 (26-83 years). Of these, 61.2% (68) were male, and 25% (17) experienced severe ARDS, resulting in a mortality rate of 47.3% (52). Ventilation settings, arterial blood gases, and chest X-ray (CXR) were evaluated on the first day of invasive mechanical ventilation and between days two and three. CXR images were scrutinized using a convolutional neural network (CNN). A binary logistic regression model for predicting C-ARDS mortality was developed based on the most influential variables: age, PaO2/FiO2 ratio (P/F) on days one and three, CNN-extracted CXR features, and age. Initial performance assessment on test data (23 patients out of the 110) revealed an area under the receiver operating characteristic (ROC) curve of 0.862 CI (0.654-0.969). Conclusion: Integrating data available in all intensive care units enables the prediction of C-ARDS mortality by utilizing evolving P/F ratios and CXR. This approach can assist in tailoring treatment plans and initiating early discussions to escalate care and extracorporeal life support. Machine learning algorithms for imaging classification can uncover otherwise inaccessible patterns, potentially evolving into another form of ARDS phenotyping. The combined features of these algorithms and clinical variables demonstrate superior performance compared to either element alone.

The flow properties of pellets or granules are crucial for further processing the drug dosage forms. Optimal compression or filling the multiparticulate dosage forms into capsules is influenced by forces between discrete particles, which could be partially characterized by flow properties. Several techniques were developed for the examination of flowability, including static and dynamic methods applying empirical studies and the up-to-date chaos theory; however newest methods seem only to be powerful with the supplement of empirical principles. Our experiments try to refine both the technique of analysis and the methods by finding new, alternative ways. Our approach to the flowability measurements was to set up a dynamic time-dependent model which combines empirical observations and the chaos theory on a geometrical basis, thus find new aspects regarding flow properties of pellets and granules that could be relevant for drug developers.