The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI), EULAR Sjogren’s Syndrome Patient Reported Index (ESSPRI), and other patient-reported outcomes (PROs), such as the visual analog scale (VAS) for symptoms and EULAR sicca score (ESS), are used to assess the disease activity of primary Sjögren’s syndrome (pSS). Recently, Clinical ESSDAI (ClinESSDAI) and Clinical Trials ESSDAI (ClinTrialsESSDAI) were developed for objective clinical disease activity indexes. However, the relationship of ClinESSDAI and ClinTrialsESSDAI with PROs as well as that between ESSPRI and other PROs and the objective parameters of glandular function in pSS have not been established. Herein, we investigated the correlation of ESSPRI and other PROs with the objective parameters of glandular function and the relationship of PROs with ClinESSDAI and ClinTrialsESSDAI in 66 patients with pSS. Correlations were calculated with Spearman’s correlation coefficient. ClinTrialsESSDAI was correlated with ESSPRI, dryness (ESSPRI-Dryness), fatigue, and pain domains of ESSPRI, VAS for oral dryness (oral-VAS), and patient’s global assessment. Although ESSPRI did not correlate with the objective parameters of glandular function, ESSPRI-Dryness, ESS, and oral- and ocular-VAS did. These results suggest that ESSPRI-Dryness, ESS, and VAS for symptoms, but not ESSPRI, reflect the glandular dysfunction and that ClinTrialsESSDAI correlates with PROs for dryness in pSS.

The current recommendation to avoid non-steroidal anti-inflammatory drugs (NSAIDs) in management of dengue virus disease is, as it was adopted earlier in COVID-19, scientifically considered of very low to low certainty. In this perspective I argue, for the first time globally, basing on real-life practice that NSAIDs might be lifesaving in early management of dengue virus disease as I originally argued and proved rightful in COVID-19. Moreover, I also argue that the Egyptian immune-modulatory Kelleni’s protocol, including nitazoxanide as an integral component, can be safely and effectively used to early manage COVID-19, human metapneumovirus, dengue virus disease, Zika virus separate or co-infections similar to what has already been experienced and published with separate or conjoined infections with SARS CoV-2, influenza, RSV and Norwalk viruses without the need of prior serological or molecular investigations to determine the causative agent.

Background: Patients undergoing dual antiplatelet therapy (DAPT) may experience recurrent gastrointestinal bleeding (GIB). We investigated the clinical characteristics and risk factors for recurrent non-variceal upper gastrointestinal bleeding (NVUGIB) in patients who had experienced NVUGIB during receiving DAPT. Methods: We enrolled patients diagnosed with NVUGIB during receiving DAPT between 2006 and 2020. Definite bleeding was confirmed by esophagogastroduodenoscopy in all NVUGIB patients. Results: A total of 124 patients were diagnosed with NVUGIB during receiving DAPT. Male was predominant (n = 103, 83.1%), bleeding mostly from the stomach (n = 94, 75.8%) and peptic ulcers (n = 72, 58.1%). After successful hemostasis of NVUGIB, 36 patients (29.0%) experienced at least one episode of recurrent upper GIB, 19 patients (15.3%) died, and 7 (5.6%) patients had a bleeding-related death. Multivariate analysis showed that age was a significant factor for re-bleeding (odds ratio [OR],1.050; 95% confidence interval [CI]:1.001-1.102, P-value:0.047), all-cause mortality (OR,1.096; 95% CI:1.020-1.178, P=0.013), and re-bleeding related mortality (OR,1.187; 95% CI:1.032-1.364, P-value:0.016). In Kaplan-Meier analysis, the cumulative probabilities of re-bleeding, death, and bleeding-related death were significantly higher in patients aged 70 and older (P=0.008, <0.001, and 0.009, respectively). Conclusion: Clinicians should be cautious about re-bleeding and mortality when elderly patients who experienced NVUGIB during receiving DAPT.Keywords: dual antiplatelet therapy; upper gastrointestinal tract; bleeding; mortality

Background: Epithelial-mesenchymal transition (EMT) is a biological process where epithelial cells lose their adhesive properties and gain invasive, metastatic, and mesenchymal properties. Maintaining the balance between epithelial and mesenchymal stage is essential for tissue homeo-stasis. Many of the genes promoting mesenchymal transformation has been identified; however, our understanding of the genes responsible for maintaining the epithelial phenotype is limited. Our objective was to identify genes responsible for maintaining the epithelial phenotype and in-hibiting EMT. Methods: RNA seq was performed using an vitro model of EMT. CTGF expres-sion was determined by qPCR and Western blot analysis. Knockout of CTGF was done using the CTGF sgRNA CRISPR/CAS9. Tumorigenic potential was determined using NCG mice. Results: Knocked-out of CTGF in epithelial ovarian cancer cells leads to the acquisition of functional characteristics associated with the mesenchymal phenotype such as Anoikis resistance, cytoskel-eton remodeling, increased cell stiffness, and acquisition of invasion and tumorigenic capacity. Conclusions: We identified CTGF is an important regulator of the epithelial phenotype, and its loss is associated with early cellular modifications required for EMT. We describe a novel role for CTGF, regulating cytoskeleton and the extracellular matrix interactions necessary for conserva-tion of epithelial structure and function. These findings provide a new window to understand the early stages on mesenchymal transformation

Introduction: Drug interactions (DDIs) represent an important clinical problem particularly in elderly patients due to polytherapy, comorbidity and physiological change in pharmacodynamic and pharmacokinetic pathways. In this study we investigated the association between drugs prescribed during hospital or clinical room discharge and the development of DDIs with drugs daily used from each patient. Methods: we performed an observational, retrospective, multicenter study on medical records of outpatients referred to general practitioners. Drug interactions (DDIs) were measured using the drug interactions probability scale. Collected data were analyzed using the Statistical Package for the Social Sciences. Results: During the study we evaluated 1,622 medical records. We recorded the development of DDIs in 10.3% of patients, of those 11.6% induced the hospitalization. Logistic regression showed an association between DDIs and sex and number of drugs used (P = 0.023). Conclusion: this real-life study shows that DDIs are common in elderly patients and physicians must take more attention after hospital discharge revaluating the treatment in order to reduce the risk of DDIs and hospitalization.

Stereotactic body radiation therapy (SBRT) is a precise and conformal radiation therapy (RT) that aims to deliver a high dose of radiation to the tumor with sparing surrounding normal tissue, making it an attractive option for head and neck cancer (HNC) patients who are not suitable for traditional long course of RT with comprehensive RT target volume. Definitive SBRT for HNC has been investigated in different settings, including early stage glottis cancer, and as alternative to brachytherapy boost after external beam RT. It also used as a primary treatment option for elderly or medically unfit patients. More recently, SBRT combination with immunotherapy in the neoadjuvant setting for HNC showed promising results. Salvage or adjuvant SBRT for HNC can be used in appropriately selected cases. Future studies are warranted to determine the optimum dose and fractionation schedules in any of these indications.

Since there are no morphological clues capable of making a pathologist suspect a possible mammary origin of a metastatic lesion without adequate clinical information, the histologic diagnosis of brain metastasis from BC is still based on the immunohistochemical expression of mammary gland markers such as GATA-3, ERs, PgRs and HER-2. The present retrospective study aimed to select purely morphological features capable to suggest the mammary origin of a metastatic carcinoma to the brain. The following histological features were collected on a series of 30 cases of brain metastases from breast cancer:(i) solid growth pattern; (ii) presence of comedonecrosis; (iii) glandular differentiation. Our results showed that most cases histologically exhibited solid growth pattern with at least focal comedonecrosis, producing an overall morphology closely reminiscent of mammary high-grade ductal carcinoma in situ. Although the above-mentioned morphological parameters are not strictly specific to a mammary origin, they may have an important diagnostic utility in leading pathologists to suspect a possible breast primary tumor and to include GATA-3, ERs, PgRs and HER-2 to the immunohistochemical panel.

Cardiovascular disease (CVD), comprising heart and blood vessel disorders, persists as the foremost contributor to global morbidity and mortality. In modern times, the intricate composition of gut microbiota has garnered significant focus, particularly for its varying impact on diverse ailments. Perturbations in gut microbiota and consequent dysbiosis have demonstrated connections with the advancement and origin of CVD, including conditions like atherosclerosis, hypertension, and heart failure. This comprehensive review delves into the pivotal role of gut microbiota in maintaining cardiovascular well-being.

We overview recent findings achieved in the field of model-driven development of additively manufactured porous materials for development of a new generation of bioactive implants for orthopedic applications. Porous structures produced of biocompatible titanium alloys by selective laser melting can present a promising material to design scaffolds with regulated mechanical properties and with capacity to be loaded with pharmaceutical products. Adjusting pore geometry, one could control elastic modulus and strength/fatigue properties of the engineered structures to be compatible with bone tissues, thus preventing the stress shield effect when replacing a diseased bone fragment. Adsorption of medicals by internal spaces would make it possible to emit the antibiotic and anti-tumor agents into surrounding tissues. We critically analyze the recent advances in the field featuring model design approaches, virtual testing of the designed structures, capabilities of additive printing of porous structures, biomedical issues of the engineered scaffolds and so on. A special attention is paid to highlight the current troubles in the field and the ways of their solutions.

BACKGROUNDː The so-called Low Cardiac Output Syndrome (LCOS) is one of the most common complications in pediatric patients with congenital heart disease undergoing corrective surgery. LCOS requires high concentrations of inotropes to support cardiac contractility and improve cardiac output, allowing for a better systemic perfusion. To date, serum lactate concentrations and central venous oxygen saturation (ScVO2) are the most commonly used perfusion markers, but they are not completely reliable to identify a state of global tissue hypoxia. The study aims to evaluate whether the venoarterial carbon dioxide difference/arterial-venous oxygen difference ratio [P(v-a)CO2/C(a-v)O2] can be a good index to predict the development of LCOS in the aforemen-tioned patients, so as to treat it promptly. METHODSː This study followed a population of 98 children undergoing corrective cardiac surgery from June 2018 to October 2020 at the Department of Cardiac Surgery of University Hospital Inte-grated Trust and their subsequent admission at the Postoperative Cardiothoracic Surgery Intensive Care Unit. During the study, central arterial and venous blood gas analysis were carried out before and after cardiopulmonary bypass (CPB) (pre-CPB and post-CPB), at admission to intensive care unit, before and after extubation and at any time of instability or modification of the patient’s clinical and therapeutic conditions. RESULTSː The data analysis shows that 46.9% of the children developed a LCOS (in line with the current literature) but that there is no statistically significant association between the P(v-a)CO2/C(a-v)O2 ratio and LCOS onset. Despite the limits of statistical significance, however, a 31% increase in the ratio emerged from the pre-CPB phase to the post-CPB phase when LCOS is present. CONCLUSIONSː This study confirms a statistically significant association between the most used markers in adult patients (serum lactate concentration, ScVO2 and oxygen extraction ratio-ERO2) measured in the pre-CPB phase and the incidence of LCOS onset, especially in patients with he-modynamic instability before surgery.

Dementia is a public health priority, in which memory impairments are prevalent and affects an individual’s daily activities. Research has tried to find ways to support memory problems of individuals with dementia. Self reference effect (SRE) has been shown to benefit memory in healthy, non-dementia group. The study aimed to investigate if SRE will improve memory performance of individuals with dementia. We used ecologically valid Ownership Procedure and the Remember/Know Paradigm to examine the Self-Reference Effect (SRE) on memory. It was hypothesised that participants living with dementia will perform differently in the recall of items that were self-referentially encoded compared to items other-referentially encoded and that the memory will be different in control participants than in those that live with dementia. The research found that self-referential processes did not have effect on memory in individuals with dementia. We suggest that impaired self-awareness may have contributed to the lack of this effect. However, we had a small sample size and these findings should be treated with caution.

Ebola virus disease (EVD) represents a global health threat. The etiological agents of EVD are 6 species of Orthoebolaviruses, with Orthoebolavirus zairense (EBOV) having the greatest public health and medical significance. EVD disease pathogenesis occurs as a result of broad cellular tropism of the virus, robust viral replication and a potent and dysregulated production of cytokines. In vivo, tissue macrophages are some of the earliest cells infected and contribute significantly to virus load and cytokine production. While EBOV is known to infect macrophages and to generate high titer virus in the liver, EBOV infection of liver macrophages, Kupffer cells, has not previously been examined in tissue culture or experimentally manipulated in vivo. Here, we employed primary murine Kupffer cells (KC) and an immortalized murine Kupffer cell line (ImKC) to assess EBOV-eGFP replication in liver macrophages. KCs and ImKCs were highly permissive for EBOV infection and IFN-γ polarization of these cells suppressed their permissiveness to infection. The kinetics of IFN-γ-elicited antiviral responses were examined using a biologically-contained model of EBOV infection termed EBOV ΔVP30. The antiviral activity of IFN-γ was transient, but a modest ~3-fold reduction of infection persisted for as long as 6 days post treatment. To assess the interferon stimulated gene products (ISGs) responsible for protection, the efficacy of secreted ISGs induced by IFN-γ were evaluated. Secreted ISGs blocked recombinant VSV expressing EBOV GP (rVSV/EBOV GP) infection, but failed to block EBOV ΔVP30. Our studies define new cellular tools for the study of EBOV infection that can potentially aid the development of new antiviral therapies. Furthermore, our data underscore the importance of macrophages in EVD pathogenesis and those IFN-γ-elicited ISGs that help to control EBOV infection.

Myelodysplastic syndromes or neoplasms (MDS) are a heterogeneous group of myeloid clonal disorders characterized by peripheral blood cytopenias, blood and marrow cell dysplasia and an increased risk for evolution to acute myeloid leukemia (AML). Non-coding RNAs, especially microRNAs and long non-coding RNAs serve as regulators of normal and malignant hematopoiesis and have been implicated in carcinogenesis. This review will present a comprehensive summary of the biology and role of non-coding RNAs, including the less studied circRNA, siRNA, piRNA, and snoRNA as potential prognostic and/or predictive biomarkers or therapeutic targets in MDS.

Abstract: The advent of Artificial Intelligence (AI) has in just a few years invested multiple areas of knowledge, also affecting the medical-scientific sector. An increasing number of AI-based applications have been developed, among which conversational AI has emerged. Among these, ChatGPT has risen to the headlines, scientific and otherwise, for its distinct propensity to simulate a 'real' discussion with its interlocutor, based on appropriate prompts. Although several clinical studies using ChatGPT have already been published in the literature, very little has yet been written about its potential application in human pathology. We conduct a systematic review following the Preferred Reporting Items for Systematic Re-views and Meta-Analyses (PRISMA) guidelines, using PubMed and Scopus as databases, with the fol-lowing keywords: ChatGPT OR Chat GPT, in combination with each of the following: Pathology, di-ag-nostic pathology, anatomic pathology. A total of 90 records were initially identified in the literature search, of which 6 were duplicates. After screening for eligibility and inclusion criteria, only 5 publications were ultimately included. The majority of publications were original articles (n = 2), followed by case reports (n = 1), letter to the editor (n = 1) and review (n = 1). Although the premises are exciting and ChatGPT is able to co-advise the pathologist in providing large amounts of scientific data for use in routine microscopic diagnostic practice, there are many limitations that need to be addressed and resolved, with the caveat that an AI-driven system should always provide support and never a decision-making motive during the anatomo-pathological diagnostic process.

A maxillary totally edentulism was rehabilitated with one-piece implants starting from pre-existing totally removable denture. A 3D digital scan of the removable denture and upper and lower arches was performed. On this basis, a prototype with optimal esthetic and functional outcomes was re-alized and turned into a custom-made radiological stent with markers. The superimposition of STL and DICOM files allowed the virtual planning of one-piece implants ideal position. The stackable templates composed of a fixed component, namely base template, and removable components, were realized. The fixed component, once secured with anchor pins to the bone, was no longer removed. The removable components, screwed to the fixed component, were used to perform the implant surgery and the immediate prosthetic loading. A base template allowed for maintaining a fixed reference during the entire workflow, improving the transition between the digital project, the surgical procedure, and the prosthetic rehabilitation.

Keywords: Antisense Oligonucleotides, Cell Penetrating Peptides, Delivery, DG9 peptide, Phosphorodiamidate morpholino oligomers (PMO), Pip, R6G.

The search for more efficacy and fewer toxic effects in cancer treatments is the main objective of research into new therapies. Vincristine (VCR) is a chemotherapeutic used in different types of tumors. Epigallocatechin gallate (EGCG) is a green tea metabolite that has shown an antineoplastic effect in different investigations, so the objective of this work was to evaluate the antitumor effect of the EGCG/VCR combination on tumor volume and survival. To achieve this objective, the solid model of lymphoma L5178Y was used in BALB/c mice with different doses of VCR, EGCG and their combination; Tumor grow and survival time were recorded. Once the tumors were obtained, they were measured and immunohistochemistry was performed for p53, Bcl2 and CD1. The results showed that the EGCG/vincristine combination had a greater antitumor effect that vincristine and EGCG. This can be partly attributed to the fact that the greatest Bcl2 inhibition was present in the combination of EGCG with vincristine. Therefore, it can be concluded that the combination of EGCG with vincristine has a better antineoplastic effect by inhibiting tumor development and increasing survival than both substances independently.

Research has shown the role of growth factors in lung cancer angiogenesis. Angiogenesis promotes lung cancer progression by stimulating tumor growth, enhancing tumor invasion, contributing to metastasis, and modifying immune system responses within the tumor microenvironment. As a result, new treatment techniques based on the anti-angiogenic characteristics of compounds have been developed. These compounds selectively block the growth factors themselves, their receptors, or the downstream signaling pathways activated by these growth factors. The EGF and VEGF families are the primary targets in this approach, and several studies are being conducted to propose anti-angiogenic drugs that are increasingly suitable for the treatment of lung cancer, either as monotherapy or as combined therapy. The efficacy results are encouraging, but a caution must be placed on the higher risk of toxicity, outlining the importance of personalized follow-up in the management of these patients.

Delineating the epidemic of vaccine injury from the coterminous condition long covid is a challenging prospect, but one with many implications not just for treatment, but also has important legal considerations for settlements of vaccine injury. The shared etiological factor of the spike protein in both vaccine injury and long covid make differentiation difficult, and while treatment is largely similar between vaccine injury and long covid, there are important distinctions. Furthermore, diagnostics are important for monitoring treatment progress and assessing the extent of subclinical vaccine injury in population having received a covid-19 vaccine. The development of rigorous diagnostics is an important step towards the recognition of both long covid and vaccine injury, as those suffering these conditions have faced immense challenges in having their conditions recognized, treated, and compensated by insurance companies or national health services.

Blood gas analysis plays a central role in modern medicine. Advances in technology have expanded the range of available parameters and increased the complexity of their interpretation. By applying user-centered design principles, it is possible to reduce the cognitive load associated with interpreting blood gas analysis. In this international, multicenter study, we explored anesthesiologists' perspectives on Visual Blood, a novel visualization technique for presenting blood gas analysis results. We conducted interviews with participants following two computer-based simulation studies: the first utilizing Virtual Reality (VR) (50 participants) and the second without VR (70 participants). Employing the template approach, we identified key themes in the interview responses and formulated six statements, which were rated using Likert scales: from 1 (strongly disagree) to 5 (strongly agree) in an online questionnaire. The most frequently mentioned theme was the positive usability features of Visual Blood. The online survey revealed that participants found Visual Blood to be an intuitive method for interpreting blood gas analysis (median 4, IQR 4-4, p<0.001). Participants noted that minimal training was required to effectively learn how to interpret Visual Blood (median 4, IQR 4-4, p<0.001). However, adjustments are necessary to reduce visual overload (median 4, IQR 2-4, p<0.001). Overall, Visual Blood received a favorable response. The strengths and weaknesses derived from these data will help optimize future versions of Visual Blood to improve the presentation of blood gas analysis results.

Embryological development of pancreas is a complex phenomenon and therefore, it can have multiple developmental aberrations. Fortunately, majority of these pancreatic ductal anomalies are asymptomatic with no clinical relevance and are incidentally detected during diagnostic cross sectional imaging or endoscopic retrograde cholangiopancreatography (ERCP) or autopsy. Occasionally, pancreatic duct anomalies can result in symptoms like abdominal pain or recurrent pancreatitis. Also, accurate pre-operative diagnosis of ductal anomalies can prevent inadvertent duct injury during surgery. Conventionally, ERCP had been used for accurate diagnosis of pancreatic duct anomalies. However, because of being invasive and associated with risk of pancreatitis, it has been replaced with magnetic resonance cholangiopancreatography (MRCP). MRCP has demonstrated high sensitivity and specificity for diagnosis of ductal anomalies which can be further improved with use of secretin enhanced MRCP. Endoscopic ultrasound (EUS) is a new diagnostic and interventional tool in the armamentarium of endoscopists and has demonstrated promising results in detection of pancreatic duct variations and anomalies. In this article, we will focus on the role of EUS in diagnosis of various pancreatic duct anomalies.

Short bowel syndrome (SBS) in adults is defined as having less than 180 to 200 cm of remaining small bowel [1–4]. Many literature sources do not provide precise epidemiological data, challenges in estimating the prevalence of SBS include its multifactorial etiology and varying definitions [1–7]. The most common pathologies leading to SBS include Crohn disease, mesenteric ischemia, radiation enteritis, post-surgical adhesions, and post-operative complications [1,2,4–6]. In advanced SBS, parenteral nutrition may be required to ensure that all vital nutrients are delivered directly through the venous system, bypassing the gastrointestinal tract [1,8–10]. In this article, we present a clinical case of a patient who underwent parenteral nutrition for four months due to SBS. The surgical team performed reconstructive re-anastomosis of both the small and large bowel, leading to the discontinuation of parenteral nutrition and the resumption of a regular diet.

Regenerative endodontic procedures (REPs) aim at recreating dental pulp tissue using biomaterials such as hydrogels. Their bioactivity is mostly linked to the nature of biomolecules or chemical compounds that will compose the endodontic hydrogel. However, many other parameters, such as hydrogel concentration, type, bioactive molecules solubility, of apex size were reported to influence the hydrogel behavior, leading to the inability to predict the clinical outcome. This lack of knowledge and the various parameters that should be considered, suggest that biological activity of endodontic hydrogel is impossible to anticipate and could hinder the bench to bedside transition. We formulated in this article our opinion that most of these parameters could be identified, described, and studied. A second part of the document lists some challenges and perspectives, including development of future mathematical models able to explain and predict the bioactivity of these endodontic hydrogel in clinic.

The purpose of this study was to determine the effects of aerobic exercise on carotid to femoral pulse wave velocity (cf-PWV), cell adhesion molecules (intracellular adhesion molecules (ICAM-1), vascular cell adhesion molecules (VCAM-1), and endothelial selectin (E-selectin), and oxidized-LDL in elderly women aged 70–85 years, and to identify the effect of and correlation with vascular stiffness. Forty participants were recruited and divided into three groups; vascular stiffness (VSG, n=14), obesity (OG, n=14), and normal (NG, n=12). All groups were given a 16-week intervention of aerobic exercise, and the data collected before and after exercise were analyzed using SPSS Ver. 23.0. Two-way repeated-measures ANOVA was used to evaluate between-group and time-dependent interaction effects. One-way ANOVA was used to evaluate between-group variations. In addition, the significance was tested using a post-hoc test (Scheffe). The within-group variations by time before and after exercise were examined using a paired t-test, and correlation analysis was performed using Pearson correlation coefficients. Simple regression analysis was performed for variables showing significant differences. The results indicated interaction effects for cf-PWV (p<.001), VCAM-1 (p<.01), E-selectin (p<.05) and oxidized LDL (p<.001). The rate of change of cf-PWV was positively correlated with that of VCAM-1 (r=.352, p<.05) and that of oxidized-LDL (r=.325, p<.05) with statistical significance. To determine the effect of the rate of change of cf-PWV on the rate of change of VCAM-1, the variables were tested, and the coefficient of determination in the regression analysis was .124, indicating that 12.4% of the tested variables fit the standard regression line. The variables for the effect of the rate of change of cf-PWV on the rate of change of oxidized LDL were also tested, and the coefficient of determination in the regression analysis was .106, indicating that 10.6% of the tested variables fit the standard regression line. Thus, the 16-week regular and consistent aerobic exercise program had significant effects on the cf-PWV, ICAM-1, VCAM-1, E-selectin, and oxidized-LDL in elderly Korean women with vascular stiffness, suggesting improvements in vascular stiffness, based on which the intervention is predicted to contribute to the prevention of vascular dysfunction by lowering the risk of cardiovascular disease due to atherosclerosis, as well as having a positive effect in the prevention of impairment of vascular endothelial cells.

Introduction: The goals of this retrospective cohort study of 129,443 persons admitted to Calgary acute care hospitals 2013-2021 were to ascertain correlations of “potentially inappropriate medi-cations” (PIMs), “potential prescribing omissions” (PPOs) and other risk factors with readmissions and mortality. Methods: Processing and analysis codes were built in Oracle Database 19c (PL/SQL), R and Excel. Results: The percentage dying during their hospital stay rose from 3.03% during the first to 7.2% during the 6th admission. The percentage dying within 6 months of discharge rose from 9.4% after the first to 24.9 after the sixth admission. Odds ratios (adjusted for age, gender and comorbidities) for readmission were the post-admission number of medications (1.16; 1.12-1.12), STOPP PIMs (1.16; 1.15-1.16); AGS Beers PIMs (1.11; 1.11-1.11) and START omissions not corrected with a prescription (1.39 (1.35-1.42). Odds ratios for mortality were post-admission number of medications (1.04; 1.04-1.05), STOPP PIMs (0.99; 0.96-1.00); AGS Beers PIMs (1.08; 1.07-1.08) and START omissions not corrected with a prescription (1.56 (1.50-1.63). START omissions corrected with a prescription correlated with a dramatic reduction in mortality (0.51; 0.49-0.53). Odds ratios for readmissions for the second through 39th admission were consistently higher if START PPOs were not corrected for the second admission (1.41; 1.36-1.46), third (1.41;1.35-1.48); fourth 1.35;1.28-1.44); fifth 1.38; 1.28-1.49); sixth (1.47;1.34-1.62) and 7th through 39th admission (1.23; 1.14-1.34). For all admissions when a pre-scription was given to correct START PPOs ORs for mortality within six months of discharge were dramatically improved (0.51; 0.49-0.53). This was also true for the second (0.52; 0.50-0.55; fourth (0.56; 0.52-0.61; fifth (0.63; 0.57-0.68); sixth (0.68; 0.61-0.76); and 7th through 39th admissions (0.71; 0.65-0.78). Conclusions: PPOs should be corrected by prescriptions and teams of family physicians, pharmacists and nurses should focus on patients’ understanding of their illnesses, medications and ability for self-care.

The BNT162b2 vaccine is globally used for preventing morbidity and mortality related to COVID-19. Cancer patients have had priority for receiving the vaccine due to their diminished immunity. This study reports the response of administering the 3rd and 4th vaccine doses to can-cer patients receiving active anti-neoplastic treatment. 142 patients have received two doses of the mRNA-based BNT162b2 COVID-19 vaccine, while 76 and 25 patients have received three and four doses, respectively. The efficacy of the humoral response following two vaccine doses was diminished in cancer patients, especially in the group of patients receiving chemotherapy. In a multivariate analysis, patients after three and four BNT162b2 vaccine doses were more likely to have antibody titers in the upper tertile compared to patients after two doses of the vaccine (odds ratio (OR) 7.62 (95% CI 1.38-42.12), p=0.02 and 17.15 (95% CI 5.01-58.7), p<0.01, respective-ly). Unlike the response after two doses, the 3rd and 4th BNT162b2 vaccine booster doses, had an increased efficacy of 95-100% in cancer patients while on active treatment. This result could be explained by different mechanisms including the development of memory B cells.

Abstract: Medication overuse headaches is a frequent phenomenon observed in individuals suf-fering from chronic headaches. It arises due to the excessive consumption of pain-relief medica-tions, resulting in the escalation and continuous persistence of headache symptoms. Nevertheless, the prevalence and distinctive characteristics of medication overuse headaches in the pediatric population have not been comprehensively explored. The primary objective of this research is to delineate the features of medication overuse headaches in children, particularly emphasizing the investigation of its epidemiology and the diagnostic patterns for headaches. We conducted a ret-rospective study by and analyzed the medical records of children and adolescents who were evaluated at outpatient pediatric headache clinic at the Bnai Zion medical center for headache during the period spanning 2007 to 2017. Our study encompassed a cohort of 1008 patients expe-riencing headaches. Among these participants, 268 individuals (26.6%) were diagnosed with mi-graine, 250 (24.8%) exhibited tension-type headaches (TTH), and 490 (48.6%) were classified as having undifferentiated headaches. Out of the whole group, 65 had chronic headaches: 35 (54%) with migraine, 20 (30%) with tension-type headaches (TTH), and 10 (15%) with undifferentiated headache of childhood, with the majority (73%) being female.In summary, medication overuse headaches are a prevalent issue among children grappling with chronic headaches. Intriguingly, they appear to be more pronounced within the tension-type headache (TTH) group compared to migraine sufferers, and exhibit a higher prevalence among females. This study underscores the significance of early detection and careful management of medication overuse headaches in pedi-atric cases, shedding light on its distinct characteristics in the realm of childhood headache disor-ders. Further research is warranted to elucidate the underlying factors contributing to the ob-served gender disparity and the distinct prevalence rates among different headache subtypes.

Background: Down Syndrome is the most well-studied aneuploidy condition in humans. It is associated with multiple disease phenotypes including cardiovascular, neurological, haemato-logical, and immunological disease processes. In this review paper we aim to discuss the research into gene expression studies performed at the fetal stage of development. Methods: A descriptive review was performed including all papers published on the PubMed database between Septem-ber 1960- September 2022. Results: In the amniotic fluid, genes such as COL6A1 and DSCR1 are affected, causing the phenotypical craniofacial changes. Other genes affected in amniotic fluid in-cluding: GSTT1, CLIC6, ITGB2, C21orf67, C21orf86 and RUNX1. In the placenta, MEST, SNF1LK and LOX were dysregulated, affecting nervous system development. In the brain DYRK1A, DNMT3L, DNMT3B, TBX1, olig2 and AQP4 were found to be dysregulated, affecting the nervous system and intellectual disability. In the cardiac tissues GART, EST2 and ERG found to be dysregulated causing secondary heart field abnormalities. XIST, RUNX1, SON, ERG and STAT1 dysregulated causing myeloproliferative disorders. Conclusions: Differential expression of genes provides clues to the genetic consequences of DS. A better understanding of these processes could eventually to lead to the development of genetic and pharmacological therapies.

Nasal nitric oxide (nNO) is a gas synthesized by the inducible and constitutive NO synthase enzyme in the airway cells of the nasal mucosa. Like lung nitric oxide, it is thought to be associated with airway inflammation in various respiratory diseases in children. The aim of our review was to investigate the current state of use of nasal nitric oxide measurement in children. A comprehensive search was conducted using the Web of Science and PubMed databases specifically targeting publications in the English language, with the following keywords: nasal NO, children, allergic rhinitis, chronic rhinosinusitis, acute rhinosinusitis, primary ciliary dyskinesia (PCD) and cystic fibrosis (CF). We describe the use of nNO in pediatric allergic rhinitis, chronic rhinosinusitis, acute rhinosinusitis, primary ciliary dyskinesia (PCD), and cystic fibrosis (CF) based on the latest literature. CONCLUSION: nNO is a noninvasive, clinically applicable test for use in pediatric allergic rhinitis, chronic rhinosinusitis, acute rhinosinusitis, PCD and CF. It can be used as a complementary method in the diagnosis of these respiratory diseases and as a monitoring method for the treatment of allergic rhinitis, acute and chronic rhinosinusitis.

Abstract Purpose: To analyze the correspondence between refractive astigmatism and corneal astigmatism in pseudophakic eyes with non-toric intraocular lenses. Setting: Yeouido St. Mary hospital, Seoul, South Korea Design: Evaluation of a diagnostic test instrument. Methods: This retrospective study included 95 eyes of 95 patients. Corneal astigmatism was measured with an automated keratometer (RK-5, Canon) and Scheimpflug tomography (Pentacam HR, Oculus). Refractive astigmatism was compared to keratometric astigmatism (based on anterior corneal measurements only), Equivalent K Reading and total corneal astigmatism (both based on anterior and posterior corneal measurements). Vector analysis was carried out by Næser’s polar value method. The accuracy was defined as the average magnitude of the vectorial difference in astigmatism (DA). Each corneal measurement was optimized in retrospect by a multiple linear regression equation between refractive and corneal astigmatism. Results: Keratometric astigmatism overestimated with-the-rule (WTR) refractive astigmatism and underestimated against-the-rule (ATR) refractive astigmatism. Several measurements based on both corneal surfaces values did not show any statistically significant difference with respect to refractive astigmatism. The mean corneal astigmatism by total corneal refractive power (TCRP) at 4.0 mm (zone/pupil) produced the lowest mean arithmetic DA and the highest percentage of eyes with a DA ≤0.50 diopter. After optimization, the accuracies of automated KA and TCRP 4.0 mm (zone/pupil) were similar. Conclusions: Total corneal astigmatism measured by the Scheimpflug tomography at 4.0 mm zone centered on pupil, accurately reflects the refractive astigmatism in pseudophakic eyes. However, the accuracy of total corneal astigmatism is not different from automated KA after optimization.

(1) Importance of problem: Breast cancer accounted for 685.000 deaths globally in 2020, and half of all cases occur in women with no specific risk factor beside gender and age-group. During last 4 decades we see a reduction by 40% of age-standardized breast cancer [1], which in turn means that the number of mastectomies performed for younger women increased, raising the need for adequate breast reconstructive surgery. Advances in oncological treatment have made it possible to limit the extent of what represents radical surgery for breast cancer, yet in the past decade, we see a marked trend toward mastectomy in breast conserving surgery eligible patients [2]. Prophylactic mastectomy has also registered an upward trend [3,4]. This trend together with new indication for breast reconstruction like chest feminization in transgender patients [5] have increased the need for breast reconstruction surgery. (2) Purpose: The purpose of this study is to analyze the types of reconstructive procedures, their indications, their limitations, their functional results and the safety profiles when used during the integrated treatment plan of the oncologic patient; (3) Methods: We conducted an extensive literature review of the main reconstructive techniques, especially the autologous procedures, summarized the findings and presented a few cases from our own experience for exemplification of the usage of breast reconstruction in oncologic patients. (4) Conclusions: Breast reconstruction has become a necessary step in the treatment of most breast cancers and many reconstructive techniques are now routinely practiced. Microsurgical techniques are considered the "gold standard", but they are not accessible to all services, from a technical or financial point of view, so pediculated flaps remain the safe and reliable option, along with alloplastic procedures, to improve the quality of life of these patients.

In the aftermath of the COVID pandemic, post-COVID-19 syndrome (PCS) remains a challenge and may continue to represent a major health problem in the future. Moreover, the influence of type 2 diabetes and being overweight on PCS remains unclear. This study aimed to assess this influence. We performed an observational study from October 2020 to July 2022, which included 466 patients (269 males and 197 females) with a median age of 65. They were hospitalized due to COVID-19 pneumonia and had persistent symptoms after 1 month of COVID-19 infection. The patients were divided into four groups according to the study objectives: patients with type 2 diabetes, overweight patients, overweight patients with type 2 diabetes, and normal-weight patients without type 2 diabetes. The clinical and demographic data collected during hospitalization and regular visits at the Community Healthcare Center dr. Adolf Drolc Maribor were analyzed. Our results showed that type 2 diabetes patients had a more difficult course of treatment and longer hospitalization. Moreover, more type 2 diabetes patients underwent rehabilitation than the other study groups. The prevailing symptoms in our patients with PCS were dyspnea and fatigue, mostly in female patients with type 2 diabetes. Our study also showed that more women with type 2 diabetes and more overweight women with type 2 diabetes suffered from secondary infections. Further, more overweight patients were treated in the intensive care unit compared to the other groups. However, our study showed an interesting result that patients with type 2 diabetes had the shortest PCS durations. Type 2 diabetes and being overweight are risk factors for PCS onset and prolonged duration. Therefore, our data that revealed a shorter duration of PCS in type 2 diabetes patients compared to the other investigated groups was unexpected. We believe that answering this question regarding the results will enable us to improve PCS treatment in general.

This prospective study aimed to evaluate the ability of point-of-care Doppler ultrasound measurements of carotid-corrected flow time and changes in corrected carotid flow time (FTc) induced by volume expansion to predict fluid responsiveness in patients undergoing robot-assisted gynecological surgery in a modified head-down lithotomy position. FTc was measured using Doppler images of the common carotid artery before and after volume expansion. The stroke volume index at each time point was recorded using the MostCare instrument. Fluid responsiveness was defined as a stroke volume index ≥10% increase after volume expansion. Half (50%) of the 52 patients responded positively. The areas under the receiver operating characteristic curves measured to predict fluid responsiveness for the corrected carotid flow time and changes in the FTc were 0.82 [95% confidence interval:0.705–0.937; P &lt; 0.0001] and 0.67 (95% confidence interval:0.520–0.815; P &lt; 0.05), respectively. The optimal cut-off value for the FTc and the change in FTc were 356.5 ms and 19.5 ms, respectively. FTc is a more reliable predictor of fluid responsiveness than FTc induced by volume expansion in gynecological patients undergoing robot-assisted laparoscopic surgery in the modified head-down lithotomy position.

Children with history of prematurity are at higher risk of complications, comorbidities and iron deficiency. In this study we assess the prevalence of restless sleep disorder, as well as that of periodic leg movements during sleep (PLMS) in these children. Retrospective chart review of sleep studies in children aged 1-18 years, with history of prematurity. Only diagnostic studies in children without diagnosis of a genetic syndrome or airway surgery or tracheostomy were included. Three groups were compared, children with PLMS index&gt;5, children with restless sleep disorder (RSD), and children with neither elevated PLMS index nor RSD. During the study, 2,577 sleep studies were conducted. Ninety-two studies fit our criteria and were included in analysis. Median birth age was 31 weeks, interquartile range (IQR) 27-34 weeks. Thirty-two (34.8%) children were referred for restless sleep and 55 (59.8%) for snoring; after polysomnography 18% were found to have PLMS index &gt;5/hour, 14% fit the criteria for RSD. There were no statistically significant differences in polysomnographic parameters between the children with RSD, PLMS and the remaining group, except for lower obstructive apnea/hypopnea index (Kruskal-Wallis ANOVA 8.621, p=0.0135) in the RSD group (median 0.7, IQR 0.3-0.9) than in the PLMS (median 1.7, IQR 0.7-3.5), or than in the nonRSD/nonPLMS group (median 2.0, IQR 0.8-4.5). There was elevated frequency of RSD and elevated PLMS in children with history of prematurity that might be linked to the increased risk of iron deficiency in premature infants. These new results add new knowledge on the prevalence of RSD in these children.

Abstract: Background: The Hospital-at-home (HAH) model is a viable alternative for conven-tional in-hospital stays worldwide. Serum electrolyte abnormalities are common in acute pa-tients, especially in those with many comorbidities. Pathologic changes in cardiac electrophysi-ology pose a potential risk during HAH stay. Periodical Electrocardiogram (ECG) tracing is therefore advised, but few studies evaluated the accuracy and efficiency of compact, self-activated ECG devices in the HAH settings. This study aimed to evaluate the reliability of such a device in comparison to a standard 12-lead ECG. Methods: We prospectively recruited consecu-tive patients admitted to the Sheba Beyond, virtual hospital, in the HAH department, during a 3-month duration. Each patient underwent a 12-lead ECG recording using the legacy device, and a consecutive recording by a compact 6-lead device. Baseline patients’ characteristics during hospi-talization were collected. Level of agreement between devices was measured by Cohen’s Kappa coefficient for inter-rater reliability (Ϗ). Results: Fifty patients were included in the study. 26 (52%) had electrolyte disturbances. Abnormal D-dimer values were observed in 33 (66%) pa-tients, and 12 (24%) patients had elevated troponin values. We found a level of 94.5% raw agreement between devices with regards to nine of the options included in the automatic read-out of the legacy device. The calculated Ϗ was 0.72, classified as substantial consensus. The rate of raw consensus regarding ECG intervals’ measurement (PR, RR, QT) was 78.5% and the calculated Ϗ was 0.42, corresponding to a moderate level of agreement. Conclusion: This is the first report to our knowledge regarding the feasibility of using a compact, 6-Lead ECG device in the setting of HAH to be safe and bearing satisfying agreement level with a legacy, 12-lead ECG device, en-abling quick, accessible arrythmia detection in this setting. Our findings bear a promise to the future development of telemedicine-based hospital at home methodology.

Post-traumatic stress disorder (PTSD) is a debilitating mental health disorder that causes significant dysfunction in individuals. Currently, there are many approved Pharmacotherapy and Psychotherapy treatment options for PTSD, but unfortunately, half of the patients do not respond to traditional therapies. In this article, we reviewed clinical trials and research on 3,4-methylenedioxymethamphetamine (MDMA) assisted Psychotherapy in PTSD patients, its pharmacokinetics and current treatment guidelines for PTSD. Based on the results of the efficacy of MDMA assisted Psychotherapy from six phases II Randomized controlled trials. MDMA-assisted Psychotherapy for PTSD has received the “Breakthrough Therapy” designation from the FDA. MDMA can potentially reduce PTSD symptoms even in treatment-resistant cases by increasing certain neurohormones, i.e. dopamine, serotonin, norepinephrine and oxytocin. It also modulates activities in the brain regions involved in fear and anxiety. Future research is needed to show whether the advantages outweigh the disadvantages and whether its use can be integrated into available treatment options for PTSD.

The SARS-CoV-2 infection is a cause of hypoxemic acute respiratory failure, leading to frequent intensive care unit (ICU) admission. Due to invasive organ support and immunosuppressive therapies, these patients are prone to nosocomial infections. Our aim was to assess the value of daily measurements of C-reactive protein (CRP) and Procalcitonin (PCT) in the early identification of ICU-acquired infections in COVID-19 patients Methods: We undertook a prospective observational cohort study (12 months). All adult me-chanically-ventilated patients admitted for ≥ 72 hours to the ICU with COVID-19 pneumonia were divided into an infected group (n=35) and a non-infected group (n=83). Day 0 was considered as the day of the diagnosis of infection (infected group) and day 10 of ICU stay (non-infected group). The kinetics of CRP and PCT were assessed from day -10 to day 10 and evaluated using a general linear model, univariate, repeated-measures analysis. Results: 118 patients (mean age 63 years, 74% males) were eligible for the analysis. The groups did not differ in patients' age, gender, CRP, and PCT serum levels at ICU admission. However, the infected group encompassed patients with a higher severity (SOFA score at ICU admission, p=0.009) and a higher 28-day mortality (p<0.001). Before D0, CRP kinetics showed a significant increase in infected patients, whereas in noninfected it remained almost unchanged (p<0.001), while PCT kinetics did not appear to retain diagnostic value to predict superinfection in COVID-19 patients (p=0.593). Conclusion: COVID-19 patients who develop ICU-acquired infections exhibited different biomarker kinetics before the diagnosis of those infections. Daily CRP monitoring and the recognition of the CRP kinetics could be useful in the prediction of ICU-acquired infections.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths and remains a major burden on health-care systems worldwide. The incidence of HCC continues to rise globally, despite preventative efforts being made. Aims: This study aimed to investigate epidemiological changes observed in the aetiology and survival outcomes of HCC patients at Klinikum Klagenfurt am Wörthersee between 2012 and 2023. Methods: This was a retrospective, single-centre cohort observational study. Two time-periods (2012-2017 and 2018-2023) were created to enable comparison between the respective intervals. Results: More patients were diagnosed with HCC during the second time-period, proving that the incidence of HCC is rising or the referral patterns changing. The median age of diagnosis was 72.5 years (SD 8.6). Patients were on average 2 years younger in the second time-period compared to the first (p = 0.042). Alcohol remained the leading underlying aetiology of HCC and no statistically significant change was seen over time (p = 0.353). Nevertheless, a clear upward trend in the number of NASH cases was evident over time (n = 15, n = 28 respectively). Nearly half of the patient population did not have a raised AFP at the time of diagnosis. The survival time for HCC patients remained similar between time-periods, with a median overall survival time of 20.5 months (95% CI 16.8-24.2, p = 0.841), despite improvements in management strategies and the availability of new systemic treatments but more advanced stage HCC was documented in the second period. An increasing number of HCC patients without liver cirrhosis were identified during the second time-period (n = 22, n= 47 respectively, p = 0.005). NASH was the most common underlying aetiology in patients without liver cirrhosis (50%), compared to alcohol use in being the primary cause in cirrhotic patients (p < 0.001). Conclusion: HCC continues to be an important health concern in our society. The number of HCC patients without liver cirrhosis is steadily increasing, with NAFLD/ NASH, due to underlying life-style diseases playing an important aetiological role. Continued efforts should be made to prevent HCC and to screen at-risk population groups. Preventative strategies and screening techniques should be adjusted in light of the changing epidemiological landscape of HCC.

Plants belonging to the genus Irvingia are widespread across the African and Southeast Asian regions of the world. Irvingia gabonensis, Irvingia malayana, and Irvingia grandifolia are among the commonly used species in ethnomedicine, especially in Africa. Fever, scabies, toothache, inflammation, and liver and gastrointestinal disorders are among the pathological conditions that are reverted by Irvingia plants upon traditional preparations. Modern pharmacological investigations have substantiated the ethnomedicinal uses of Irvingia spp. Reports on the phytochemical analysis of Irvingia plants have revealed the presence of a number of secondary metabolites, such as flavonoids, phenolic compounds, tannins, saponins and alkaloids. Based on the foregoing, the present study provides a comprehensive evaluation of reports on the ethnomedicinal use, phytochemistry, pharmacology, and toxicity of plants from the genus Irvingia. Relevant information on Irvingia plants was mostly obtained from major scientific databases from their inception until July 2023. As a result, more than forty compounds have been identified in Irvingia spp. proving the abundance of secondary metabolites in these plants. Reports have pointed out modern pharmacological activities, such as antiprotozoal, antimicrobial, antioxidant, antidiabetic, anti-inflammatory, and hepatoprotective activities. The present study provides more insights for the successful utilization of Irvingia plants and may guide further research on their therapeutic potential in the treatment of various diseases.

This study aimed to investigate the characteristics and outcomes of patients who underwent per-cutaneous coronary intervention (PCI) and visited an emergency department (ED) with chest pain in Saudi Arabia. A retrospective analysis of patient data was conducted, focusing on demographics, risk factors, pain assessment, triage, diagnostic testing, and management. The results revealed a young adult population (40-59 years old) at risk for coronary heart disease (CHD), highlighting the need for increased awareness and education. Gender differences in cardiovascular disease (CVD) presentation and underdiagnoses in women also require attention for effective prevention and treatment. Accurate pain assessment during triage was found to be essential to prevent mistriage and negative patient outcomes. Chest pain and shortness of breath were common symptoms, emphasizing the importance of recognizing acute myocardial infarction (AMI) symptoms for proper triage, diagnostic testing, and prompt treatment. The study identified modifiable CVD risk factors, including diabetes (51.1%), hypertension (43.8%), and smoking (25.9%), stressing the importance of lifestyle modifications to reduce CVD risk. Saudi Arabia faces significant challenges in addressing cardiovascular disorders, but efforts to improve healthcare access and establish specialized centers are promising. In conclusion, this study underscores the need for increased awareness of CHD among young adults, accurate pain assessment during triage, and lifestyle modifications to address modifiable CVD risk factors. Furthermore, healthcare teams must stay updated on new chest pain guidelines in the ED and prioritize early detection of implicated arteries and prompt reperfusion. Further research investigating chest pain patient triage and assessments across Saudi Arabia is recommended to identify areas of improvement and implement necessary changes in clinical practice.

Inflammatory Bowel Disease (IBD) presents distinct challenges during pregnancy due to its influence on maternal health and pregnancy outcomes. This literature review aims to dissect the existing scientific evidence on pregnancy in women with IBD and provide evidence-based recommendations for clinical management. A comprehensive search was conducted across scientific databases, selecting clinical studies, systematic reviews, and other pertinent resources. Numerous studies have underscored an increased risk of complications during pregnancy for women with IBD, including preterm birth, low birth weight, neonates small for gestational age, and congenital malformations. Nevertheless, it's evident that proactive disease management before and throughout pregnancy can mitigate these risks. Continuation of IBD treatment during pregnancy and breastfeeding is deemed safe with agents like thiopurines, anti-TNF, vedolizumab, or ustekinumab. However, there's a call for caution when combining treatments due to the heightened risk of severe infections in the first year of life. For small molecules, their use is advised against in both scenarios. Effective disease management, minimizing disease activity, and interdisciplinary care are pivotal in attending to women with IBD. The emphasis is placed on the continual assessment of maternal and infant outcomes and an expressed need for further research to enhance the understanding of the ties between IBD and adverse pregnancy outcomes.

Due to the low content, few studies are focused on the essential oils (EOs) of Phlomoides rotata (Benth. ex Hook. f.) Mathiesen (syn. Lamiophlomis rotata (Benth.) Kudô. This plant has been used to treat rheumatic arthritis and grasserie in China. However, such EOs may have important pharmacological activities such as anti-cancer. To identify the chemical markers (CM) in the EOs and evaluate their antioxidant activities (AAs), we firstly conduct a thoroughly investigation on their chemicals and AAs, to the best of our knowledge. Light yellow EOs with fresh and elegant smell are obtained by hydro-distillation with average yield 0.11% (volume mL/weight g). The crystals are separated from the EOs through cryoprecipitation, respectively. A total of 81 components are qualified and quantified in the EOs, crystals and EOs removed crystals, in which 44 ones are first reported. As for content, the main compounds are long-chain fatty acids (FAs) and their esters. The most abundant one n-hexadecanoic acid (palmitic acid, PA) accounting for 43.15-54.8%, 58.49-64.57% and 15.9-41.1%, in the EOs, crystals and EOs removed crystals, respectively. Seven compounds including PA, tetradecanoic acid, linoleic acid, oleic acid, methyl hexadecanoate, hexahydrofarnesyl acetone and phytol can be chosen a the CMs in these EOs. The AAs are evaluated through in vitro assays. PA presents pro-oxidant activities in a concentration dependence manner. Usually, the EOs removed crystals demonstrate stronger AAs, and the crystals demonstrate weaker AAs compared with that of the corresponding EOs, which is related to the different content of PA in these samples. This study can give some hints for the utilization of such EOs which are abundant in FAs such as PA.

To learn what mothers know on newborn bloodspot screening (NBS), the procedure, and sources used, a pilot study was performed. An online questionnaire was developed, with a first part fo-cused on characteristics and the NBS procedure, a second on knowledge, information sources, and health care providers (HCP). This questionnaire was accessible until 200 answers were received. Characteristics of respondents were representative for the population. Mothers recalled verbal consent in 69.5%, 12.5% did not, 18% stated that no consent was requested. The ‘knowledge’ part contained 12 closed questions, 5 multiple-choice questions on sources, and assessment (5-point Likert) of the information transfer. The mean knowledge level was 7.2/12. Screening concepts (consequences, likelihood, sensitivity, carrier) and absence of notification of normal findings were well known. The fact that NBS is not compulsory and post-analysis sample handling were poorly known. Key HCPs were midwifes (80.5%) and nurses (38.5%). When the leaflet (44%) was pro-vided, the majority read it. Mean Likert scores were 3.36, 3.38, 3.11 and 3.35 (clarity, timing ap-propriateness, sufficiency, usefulness). The knowledge level and consent practices were reasonable well. Key HCP were midwives and nurses, leaflets were supporting. This should enable a quality improvement program to a sustainable NBS program in Flanders.

In the Emergency Department (ED), pain is one of the symptoms that is most frequently reported, making it one of the most significant issues for the emergency physician, but is frequently under treated. Intravenous (IV), oral (PO), and intramuscular (IM) delivery are the standard methods for administering acute pain relief. Firstly, we compared the safety and efficacy of IN analgesia to other conventional routes of analgesia to assess if IN analgesia may be an alternative for the management of acute pain in ED. Secondary, we analyzed the incidence and severity of adverse events (AEs) and rescue analgesia required. We performed a systematic review-based keywords in Pubmed/Medline, Scopus, EMBASE, the Cochrane Library and Controlled Trials Register finding only twenty randomized Clinical trials eligible in the timeline 1992-2022. A total of 2098 patients were analyzed and compared to intravenous analgesia showing no statistical difference in adverse effects. In addition, intranasal analgesia also has a rapid onset and quick absorption. Fentanyl and ketamine are two intranasal drugs that appear promising and may be taken simply and safely while providing effective pain relief. IN is simple to administer, non-invasive, rapid onset and quick absorption; it might be a viable choice in a variety of situations to reduce patient suffering or delays in pain management. Analgesia needs to be tailored to each patient's features and type of pain: IN Fentanyl and Ketamine look promising and may be administered easily and safely while providing effective pain relief.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects both the upper and lower motor neurons in the nervous system, causing muscle weakness and severe disability. The progressive course of the disease reduces the functional capacity in the affected patients, limits daily activities and leads to complete dependence on caregivers, ultimately resulting in a fatal outcome. Respiratory dysfunction mostly occurs later in the disease and is associated with a worse prognosis. 46 participans were included in our study, with 23 patients in ALS group and 23 individuals in the control group. The ultrasound examination of the phrenic nerve (PN) was performed by two authors using a high-resolution "Philips EPIQ 7" ultrasound machine with a linear 4-18 MHz transducer. Our study revealed that the phrenic nerve is significantly smaller on both sides in ALS patients compared to the control group arba controls (p < 0.001). Only one significant study on PN ultrasound in ALS, conducted in Japan, also showed significant results (p < 0.00001). These small studies are particularly promising, as they suggest that ultrasound findings could serve as a additinioal diagnostic tool for ALS

Background: The COMT gene polymorphism is associated with neurological and psychiatric disorders and pain perception. This study aimed to determine the relationship between the COMT (catechol-O-methyltransferase) gene polymorphism, pain perception in parturients with inhaled nitrous oxide during labour, and anxiety as a personality trait. Methods: A total number of 181 woman who chose vaginal birth were enrolled in this study. To present the difference in pain perception, the parturients were divided into one group (n=80) that chose labour analgesia with inhaled nitrous oxide (50% nitrous oxide and 50% oxygen) and one group without analgesia. The blood samples were taken during the pregnancy as a part of routine pregnancy controls in the hospital. The COMT gene polymorphism was detected with the PCR technique. Pain perception of labouring women was self-evaluated two times according to the VAS (Visual Analogue Scale) and anxiety as a personality trait was determined with STAI-T (State Trait Anxiety Inventory). Pain perception as well as anxiety were compared according to COMT genotypes. Results: In the 181 pregnant women there were 40 women (22%) of wild homozygotes (GG) of COMT, 95 women (53%) of mutant heterozygotes (GA), and 46 women (25%) of mutant homozygote (AA). A negative association of pain perception with the GA (mutant heterozigote) polymorphism of the COMT gene versus the wild type (GG polymorphism) was observed. The GA polymorphism of the COMT gene was associated with 0.46 units lower pain perception compared to the wild type (GG). The anxiety trait score in group AA was lower than in groups GA and AA. The difference reached statistical significance only when comparing AA versus GA (P&gt;0.042). Analgesic efficacy of nitrous oxide was noticed in 22% of labouring women who reported moderate pain (VAS score 4-7). Conclusions: The COMT gene polymorphism was associated with pain perception and anxiety among labouring women. The COMT gene polymorphism GA was associated with negative pain perception among labouring women. Nitrous oxide showed statistical significance in anxiolytic efficacy during labour in women with mild anxiety as a personality trait. Anxiolytic efficacy of nitrous oxide has shown better efficacy in labouring women with the COMT gene polymorphism AA.

Major depressive disorder (MDD) is one of life-threatening disorders that is prevalent worldwide. The evident etiology of this disease is still poorly understood. Therefore, a possible mechanism is used to evaluate the antidepressant effect. Nowadays, herbal medicine is gaining more interest as an alternative antidepressant. Oroxylum indicum, which is used in traditional medicine and contains a potential antidepressive compound, baicalein, has an antidepressive property. In vitro inhibitory effect on monoamine oxidase-A (MAO-A) enzyme was used to preliminarily screen the antidepressant effect of the O. indicum seed (OIS) extract. Mice were subjected to unpredictable chronic mild stress (UCMS) for 6 weeks and daily administration of the OIS extract started from week 4. The mechanisms involved in antidepressive activity were investigated. The OIS extract significantly alleviated anhedonia and despair behaviors in UCMS-induced mouse model via two possible pathways: (i) normalize the HPA-axis function by restoration of negative feedback (decreased FKBP5 and increased GR expressions) and reduction of glucocorticoid-related negative gene (SGK-1), (ii) improve neurogenesis by escalation of BDNF and CREB expression in the hippocampus and the frontal cortex. HPLC analysis of the extract showed the presence of All the results obtained from this study emphasize its potential as an effective and novel alternative treatment for MDD.

Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) and is considered one of the leading causes of mortality. Multiple immunological pathways are involved in the pathogenesis of SLE, which makes it imperative to deepen our knowledge about this disease's immunopathological complexity and explore new therapeutic targets. Since an altered redox state contributes to immune system dysregulation, this document briefly addresses the role of oxidative stress (OS), oxidative DNA damage, antioxidant enzymes, mitochondrial function, and mitophagy in SLE and LN. Although adaptive immunity's participation in the development of autoimmunity is undeniable, increasing data emphasize the importance of innate immunity elements, particularly the Toll-like receptors (TLRs) that recognize nucleic acid ligands, in inflammatory and autoimmune diseases. Here, we discuss the intriguing role of TLR7 and TLR9 in developing SLE and LN. Also included are the essential characteristics of conventional treatments and some other novel and little-explored alternatives that offer options to improve renal function in LN.

Diabetes mellitus is a widespread chronic metabolic disorder demanding regular blood glucose level surveillance (BGLs). Current invasive techniques, such as finger-prick tests, often result in discomfort for patients, leading to infrequent monitoring and potential health complications. The primary objective of this study was to design a novel, portable, non-invasive system for diabetes detection using breath samples, named as DiabeticSense, an affordable digital health device for early detection, encouraging immediate intervention. The device employed MOSFET-based electrochemical sensors to assess volatile organic compounds in breath samples, whose concentrations differ between diabetic and non-diabetic individuals. The system merged body vital signs with sensor voltages obtained by processing breath sample data to predict diabetic conditions. Our research used readings from 100 patients at a nationally recognised hospital to form the dataset. Data was then processed 10 using a Gradient Boosting Classifier model, and performance was cross-validated. The proposed system attained a promising accuracy of 86.6%, marking an improvement of 20.72% over an existing regression technique. The developed device introduces a non-invasive, cost-effective, and user-friendly solution for preliminary diabetes detection. It has the potential to increase patient adherence to regular monitoring.

Objective: This study aimed to validate the use of liquid phenol-based chemical peeling therapy for cervico-vaginal intraepithelial neoplasia (CIN and VaIN), with the goal of circumventing obstetric complications associated with surgical treatment. Methods: A total of 483 eligible women diagnosed with CIN and/or VaIN participated in this study. Participants underwent phenol-based chemical peeling therapy every 4 weeks until disease clearance. Disease clearance was determined by negative Pap tests for four consecutive weeks. HPV genotyping was conducted at the onset of the study and after disease clearance in select cases. Results: Among the 476 participants (excluding those with cancer), the number of treatment sessions until CIN/VaIN clearance ranged from 2 to 49 (median = 7 sessions). Forty-five participants (9.4%) underwent surgical treatments. Seven participants (1.5%) experienced recurrence, presenting with CIN2/VaIN2 or worse lesions; of these, three underwent LEEP, while four repeated the chemical peeling therapy. No obstetrical complications were noted among the 98 pregnancies following this therapy. The findings suggest that phenol-based therapy is safe and effective for CIN, although it requires numerous and lengthy treatments. Factors associated with resistance to this therapy include immune suppression, high-grade lesions, multiple HPV type infection, and direct or passive smoking.

Impressively increasing availability of the mechanical circulatory/cardiac support systems (MCS) worldwide, together with the deepening of the knowledge of critical care medical practitioners, have inevitably led to the discussion about further improvements of intensive care associated to MCS. An appealing topic of the left ventricle (LV) overload related to VA ECMO support endangering myocardial recovery is being widely discussed within the scientific community. Unloading of LV leads to the reduction of LV end-diastolic pressure, reduction of pressure in the left atrium and decrease of the LV thrombus formation risk. Consequently, better conditions for myocardial recovery, with comfortable filling pressures and better oxygen delivery/demand ratio are achieved. The combination of VA ECMO and Impella device, also called ECPELLA seems to be a promising strategy which may bring the improvement of CS mortality rates. The series of presented trials and meta-analyses clearly showed potential benefits of this strategy. However, the ongoing research has brought a series of new questions, as whether Impella itself is the only appropriate unloading modality, or any other approach to unload LV would be beneficial in the same way? Benefits and potential risks of LV unloading and its timing are being discussed in current review.

We aimed to investigate the clinical results following poor-quality embryo transfer and the parameters to foresee the prognosis. In this study, 2123 cycles that had day 3 and day 5 single-fresh embryo with a poor-quality embryo transfers and a good-quality embryo transfers were compared. The cycles according to transfer day were evaluated by conducting a subgroup analysis. The correlation between all the obtained demographic characteristics, controlled ovarian stimulation parameters and cycle results were analysed. Clinical pregnancy was established in 53 patients that underwent transfer in the poor-quality embryo group (14.9%). Of these patients, 36 had live birth (live birth rate per clinical pregnancy 67.9%). In cleavage-stage embryos, live birth rates per clinical pregnancy were higher in poor-quality blastocyst transfer. When analysing the factors affecting live births in poor-quality embryo group, as the total gonadotropin dose increases, the probability of live birth decreases, as in the probability of hCG positivity. In conclusion; although the probability of pregnant is low, when clinical pregnancy is established, there is a high chance of having a live birth after poor-quality embryo transfers. This could be regarded as an acceptable option in cycles when only poor-quality embryos were available.

This article explores the relationship between metabolic syndrome and cardiovascular disease, providing a comprehensive overview of its risk factors and prevalence. Metabolic syndrome, characterized by a cluster of interconnected risk factors, significantly increases the likelihood of developing cardiovascular disease and type II diabetes. The study, conducted over a one-year period, involved 117 patients with ages between 30 to 79 years old. Various elements such as gender, age, education level, background, smoking, alcohol consumption, dietary aspects, physical activity, and their contribution in developing the metabolic syndrome, were analysed.Central adiposity and high blood pressure emerged as prominent elements of the condition. The findings underscore the importance of a healthy lifestyle in the prevention and management of metabolic syndrome. Encouraging regular physical activity, maintaining a balanced diet, rich in fresh vegetables and fruits, and avoiding harmful behaviours, such as smoking or alcohol consumption, are essential in reducing the risk of metabolic syndrome and its associated cardiovascular complications. The study highlights the need for public health initiatives, as well as individualized preventive strategies to combat the rising prevalence of metabolic syndrome. Through promoting awareness of its risk factors and implementing effective interventions, healthcare professionals can contribute to better cardiovascular health worldwide. Further research in this area will continue to enhance our understanding of the metabolic syndrome and refine preventive and therapeutic approaches for its management.

There are several pathologies that can change the anatomy of the otic capsule and that can distort the bone density of the bony structures of the inner ear, but otosclerosis is one of the most frequent. Similar behavior has been shown in patients affected by osteogenesis imperfecta (OI), a genetic disease due to a mutation in the genes coding for type I (pro) collagen. In particular, we note that otosclerosis and OI can lead to bone resorption creating pericochlear cavitations in contact with the internal auditory canal (IAC). In this regard, in our experience we have collected 5 cases presenting this characteristic and their audiological data and clinical history were analyzed. This feature can be defined as a potential cause of a third-window effect, because it causes an energy loss during the transmission of sound waves from the OW away from the basilar membrane.

The surgical extraction of the impacted third molar is frequently associated with several complications. The purpose of this study is to assess how two different surgical protocols affect post-operative complications during the extraction of the lower third molars. In order to compare and evaluate two different techniques (triangular flap vs envelope flap), and the relative post-extraction complications, two groups of 150 patients each, underwent to surgical third molar extraction and 60 days of follow-up. A complication rate founded in two groups was respectively 14,00% in group A and 17,33% in group B. There was a strong association between smoking (OR:2.8) and the use of oral contraceptives (OR:1.75) with complications. The age and sex-related incidence of complications in hard tissue healing finds great variability in the literature; the analysis performed on our data did not show a statistically significant association between them. Even though related to a higher incidence of transient changes in sensitivity, it was found that the envelope flap saw a lower percentage of complications. There is still no clarity on which is the best protocol for the extraction of the lower third molar, and the choice often depends on the surgeon’s experience.

Postprandial hyperlipidemia showing postprandial increase in serum triglyceride (TG) is atherogenic and associated with the development of coronary artery disease (CAD). To diagnose postprandial hyperlipidemia, the oral fat loading test (OFLT) should be performed, however, this test is very time-consuming and is difficult to perform. Ele-vated serum TG levels reflect an increase in TG-rich lipoproteins (TRL) such chylomi-crons (CM), very low-density lipoproteins (VLDL) and their remnants (CM remnant [CMR] and VLDL remnant [VLDLR]). Understanding of elevation in CMR and/or VLDLR can lead us to understand the existence of postprandial hyperlipidemia. The measurements of apo B48 which is a constituent of CM and CMR, non-fasting TG which includes TG content in all lipoproteins including CM and CMR, non-high-density lipoprotein-cholesterol (non-HDL-C) which includes TRL and low-density lipoprotein, and remnant cholesterol, are useful to suspect the existence of postprandial hyperlipidemia. Postprandial hyperlipidemia is observed in patients with familial type III hyperlipoproteinemia, familial combined hyperlipidemia, chronic kidney disease, metabolic syndrome and type 2 diabetes. Postprandial hyperlipidemia is closely related to postprandial hyperglycemia, and insulin resistance may be an in-ducing and enhancing factor for both postprandial hyperlipidemia and postprandial hyperglycemia. Remnant lipoproteins and metabolic disorders associated with post-prandial hyperlipidemia have various atherogenic properties such as induction of in-flammation and endothelial dysfunction. A healthy diet, calorie restriction, weight loss and exercise, positively impact postprandial hyperlipidemia. Anti-hyperlipidemic drugs such pemafibrate, bezafibrate, ezetimibe and eicosapentaenoic acid have shown to improve postprandial hyperlipidemia. Anti-diabetic drugs including metformin, alpha-glucosidase inhibitors, pioglitazone, dipeptidyl-peptidase-4 inhibitors and glu-cagon like peptide 1 analogues, have shown to ameliorate postprandial hyperlipidemia. Although sodium glucose cotransporter-2 inhibitors have not been proven to reduce postprandial hyperlipidemia, they reduced fasting apo B48 and remnant lipoprotein cholesterol. In conclusion, it is important to appropriately understand the existence of postprandial hyperlipidemia and to connect it to optimal treatments.

Background and Objectives: Proper use of oral anticoagulants is crucial in the management of non-valvular atrial fibrillation (AF) patients. Left atrial appendage closure (LAAC) may be considered for stroke prevention in patients with AF and contraindications for long-term anticoagulant treatment. We aimed to assess the anticoagulation status and LAAC indications in patients with AF from HECMOS (Hellenic Cardiorenal Morbidity Snapshot) survey. Materials and Methods: HECMOS was a nationwide snapshot survey of cardiorenal morbidity in hospitalized cardiology patients. HECMOS used an electronic platform to collect demographic and clinically relevant information from all patients hospitalized on March 3, 2022, in 55 different cardiology departments. In this substudy, we included patients with known AF without mechanical prosthetic valves and moderate to severe mitral valve stenosis. Patients with prior stroke, previous major bleeding, poor adherence to anticoagulants, and end-stage renal disease were considered candidates for LAAC. Results: Two hundred fifty-six patients (mean age 76.6±11.7, 148 males) were included in our analysis. Most of them (n=159; 62%) suffered from persistent AF. Mean CHA2DS2-VASc score was 4.28±1.7, while mean HAS-BLED score was 1.47±0.9. Three out of 3 patients with a CHA2DS2-VASc 0 or 1 (female) received improperly anticoagulants. Sixteen out of 18 patients with a CHA2DS2-VASc 1 or 2 (female) received anticoagulants. Thirty-three out of 235 patients with a CHA2DS2-VASc &gt; 1 or 2 (for female) did not receive improperly anticoagulants. Among 221 under anticoagulant therapy, 191 (86.4%) received non-vitamin K antagonist oral anticoagulants (NOACs) and 30 (13.6%) received vitamin K antagonists. Relative indications for LAAC were present in 64 patients with NVAF (60 had only one risk factor and 2 had two concurrent risk factors). In detail, 36 had a prior stroke, 17 patients had a history of major bleeding, 15 patients reported poor or no adherence to the anticoagulant therapy and 5 had eGFR&lt; 15 ml/min/1.73m2. Moreover, 33 had a HAS-BLED score ≥3. No LAAC treatment was recorded. Conclusions: Anticoagulation status was nearly optimal in a high thromboembolic risk population of cardiology patients, mainly treated with NOACs. One out of four AF patients should be screened for LAAC.

Chronic Limb Threatening Ischemia (CLTI) represents the end stage form of peripheral arterial disease (PAD) and is associated to very poor prognosis with high risk of limb loss and mortality. It can be considered very similar to a terminal cancer disease reflecting a large impact on quality of life and healthcare costs. The aim of this study is to offer an overview of the relationship between CLTI, limb salvage and mortality with a focus on the need of a fast-track team-based management, that’s a driver to achieve better survival results. This review can be useful to improve management of this growing impact disease, and promote standardisation of care and communication between specialist and non-specialist health care professionals.

Glaucoma secondary to Peters' anomaly (PA) is an important factor affecting visual prognosis, but there are few reports on it. This study aimed to investigate the characteristics of glaucoma asso-ciated with PA and glaucoma surgery outcomes. This retrospective study included 31 eyes of 20 patients with PA. PA was classified into three stages: Stage 1, with a posterior corneal defect only; Stage 2, a corneal defect with iridocorneal adhesion; and Stage 3, a corneal defect with lens ab-normalities. The associations between glaucoma and anterior segment dysgenesis severity, visual prognosis, and glaucoma surgery outcomes were analyzed. Sixteen eyes of 10 patients developed glaucoma. Stage 1 PA had no glaucoma, 52% of Stage 2 had glaucoma, and 75% of Stage 3 had glaucoma. Of the 16 eyes with glaucoma, 11 underwent surgery. Eight of these 11 eyes achieved intraocular pressure (IOP) control. Five of the nine eyes that underwent trabeculotomy (TLO) succeeded, and none had corneal staphyloma. Three of the four eyes for which TLO was ineffective had corneal staphyloma (P=0.0331). Patients with PA are more likely to develop glaucoma as anterior segment dysgenesis progresses, and the effect of TLO is limited if corneal staphyloma is present.

Area covered: These drugs, particularly calcineurin inhibitors, have very narrow therapeutic windows, i.e., they have numerous drug-related side effects. Herein, we focus on the most frequent immunosuppressive drug-related side effects that we encounter in kidney-transplant recipients: namely nephrotoxicity, post-transplant diabetes mellitus, leukopenia, anemia, dyslipidemia, mouth ulcers, hypertension, and viral reactivations (cytomegalovirus and BK virus). However, other therapies that are used after kidney transplantation, e.g., valcancyclovir, may also contribute to adverse events such as leukopenia. For each side-effect, we suggest how it can be prevented and how to treat it when present.

A large body of evidence, replicated in many mouse models of Alzheimer Disease (AD), demonstrated the therapeutic efficacy of oral rapamycin. Administration of m-TOR inhibitors (mTOR-Is), early after the clinical onset, greatly diminished cognitive impairment, amyloid angiopathy, intracellular beta Amyloid and neurofibrillary tangles load. The daily intake of rapamycin has always been 2.24g/Kg/24h. In humans the maximal tolerated oral dose is a few milligrams/day, and at this dosage patients are severely immunosuppressed. Thanks to rapalogs’ scarce CNS-related side effects, we administered intracerebroventricularly (ICV) high doses of the mTOR-I everolimus in a mouse model of AD (3xTg-AD) without significant systemic effects. The instability of the liquid formulation at body temperature (BT) made the treatment very short. Nevertheless, the efficacy of the treatment was high and much longer lasting than expected. In order to set up a thermostable, translational liquid formulation of mTOR-Is, we loaded everolimus in distearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG2000) micelles by the thin layer method. The formulation we obtained maintained over 95% of activity after 14 days at BT. We can envision short, potentially periodic ICV treatments in AD patients which replicate results obtained on animal models. The treatment could benefit also Tuberous Sclerosis and Multiple Sclerosis patients.

This paper presents the case of a 75-year-old female with an extensive lesion located in the hard palate. Intraoral examination revealed an exophytic white lesion that extended from the entire left maxillary alveolar ridge to the palate beyond the midline. A thorough clinical, radiological, and histopathological examination confirmed the diagnosis of oral verrucous carcinoma.

For several millennia, doctors and healers used therapeutic ingredients extracted from minerals, plants, and animals. Among the active remedies derived from animals, the placenta was among the most popular ones. The use of placenta-based remedies has retained its significance in our time. The placenta-based therapeutics are indicated for stimulating immunity, wound healing, reduction of skin pigmentation, treatment of various patients suffering from gynecological disorders, etc. By the beginning of the 21st century, the majority of specific functions and chemical ingredients of the placenta were identified and described. However, only now active proteins and peptides with molecular weight of about ten kDa were revealed. Presumably, they play an essential role during the therapeutic application of placental extract. Hopefully, this discovery will start a new era in the research and clinical application of organotherapeutic remedies, including placenta.

Background: Cataract and Age-related Macular Degeneration are two characteristic diseases of the so-called elderly age (75-90 years and older). Both determine an important visual impairment, so it is often difficult to understand how much of the visual loss is given by the cataract opacities and how much by the degeneration of the macula and this assumes a relevant medico-legal query in clinical practice. Methods: From that pool we randomized in group 735 eyes with wAMD (males 328, females 407) Average age: 76.23±13.87 years, and in Group 819 eyes without clear signs of wAMD (males 361, females 451) Average age: was 75.88±18.21 years to randomize them we used the online randomization program (http://www.graphpad.com/quickcalcs/index.cfm) selecting random numbers and then randomly assign subjects to groups to undergo our observational study. All patients were examined with full ophtalmological visit including Best Corrected Visual Acuity (with Bailey-Lawson Chart), Anterior Segment examination, Fundus Examination, in all cases with wAMD was also performed OCT. ANOVA multifactorial statistical analysis was drawn. Results: number of patients with unsatisfactory surgery is significantly higher in the group of AMD patients, and this is easily understandable from what has been said above, but I would like to underline that in most patients there are very positive results, therefore cataract surgery is also indicated in AMD patients. Conclusions: Cataract surgery has a positive impact on the patient's life in most cases, you shouldn't be afraid to operate. However, it is necessary to find surgical measures capable of minimizing the consequences of the intervention on the retina.

The use of antibiotics grown promoter has been banned, due led problems with drug residues in animal products and increased bacterial resistance. For several reasons there is a growing interest in the scientific community in immunoglobulin Y as antibiotic alternative and their oral administration in the polyclonal antibody (pAb) format, to maintain animal health and performance, do not require IgY purification for large-scale production, resulting in protein impurities and high concentration of biotin in the samples. The signal amplification through non-covalent interaction of biotin with streptavidin has been extensionally used by many laboratories for several diagnosis diseases and scientific research in enzyme-linked immunosorbent assay (ELISA). However, the riches sources of biotin as egg yolk, leading to high biotin concentrations in samples, harming the accuracy of diagnostic and proteins concentrations tests. This study aimed to evaluate the biotin influence on measurement of Immunoglobulin Y in egg yolk freeze dried samples from immunized laying hens by immunoassays using biotin-avidin/streptavidin. The IgY concentration changed down in immunoassays using biotin-avidin/streptavidin. The detection of IgY in yolk samples by ELISA using streptavidin–biotin binding as part of the assay methodology requires some technology to neutralize high concentration of biotin on sample or more steps beyond delipidation to isolate the target protein. Otherwise, an ELISA without the use of streptavidin-biotin binding would be more advisable to avoid biotin and targets protein relationship and prevent biotin interference on results.

Introduction: Intimate partner violence occurring during pregnancy has a similar prevalence as usual obstetrical disorders routinely screened for. Referenced publications insist on the importance of adequate screening but the proper course of action has yet to be defined. Aim of study: We qualitatively explored the different resources and concepts that emerge from the discourse of maternity staff across professions. Material and methods: We led a semi structured interview with professionals included following their involvement with preselected patients. Nine professionals provided a sample of 19 interviews. The data was analysed using IPA methodology. Results We highlight the investigative importance of navigating the patient’s initial demand or lack thereof and the baby’s importance within, mindful of mechanisms of maternal disqualification. Creating an atmosphere prone to patient empowerment was the final theme to emerge from the study as the most beneficial tactic both in the short and long term. Conclusion: HCPs need to enable patients’ trust on a personal and an institutional level. As well as empowering the patient in the moment and respecting their values and choices, HCPs also convey the stability of the institution that has to become a reference of refuge and assistance for patients from their pregnancy onwards.

Background: Schizophrenia is a mental disorder associated with inflammatory and oxidative stress markers such as lactate; in addition, the rate of physical inactivity in this population is very high, which leads to physical and metabolic alterations. Aims: This study measured the effect of assisted physical exercise over lactate levels in schizophrenia. Methods: Stable outpatients with schizophrenia and a group of Healthy controls received two different programs of Physical exercise (Aerobic and Functional) in a clinical trial. Results: Patients had higher lactate compared to healthy controls before and after intervention, and had higher rate of lactate increase after activity. The finding of increased lactate in schizophrenia detected before and after physical exercise deserve further attention in biomarker studies and in the development of physical rehabilitation in schizophrenia, suggesting different profile of oxidative metabolism after physical exercise. Basal increased lactate may reflect mitochondrial dysfunction or metabolic dysregulation, and the higher rate of increase may reflect a different metabolic and oxidative process. Conclusion: The finding is in line with recent studies as surrogate of mitochondrial dysfunction in schizophrenia and points to the need of additional studies on mitochondrial activity in schizophrenia, and to additional care in the design of physical interventions in schizophrenia.

During the preclinical research process, multiple factors can be difficult to implement without the careful consideration and planning of each step. As research has become more advanced with the use of increasingly complex technology, animal models have also become essential for understanding the potential impact of devices, drug therapies, and surgical techniques on humans before clinical trials are conducted. The use of an in vivo animal model is a key and necessary step in the progression of preclinical research studies that will lead to future medical inventions and innovation. Here, we describe the three phases of effectively designing a preclinical research protocol: the research, preprocedural planning, and experimental phases. Furthermore, we provide researchers with guidance through these phases and discuss important considerations.

One of the most critical aspects in introral impression is the detection of the finish line, in particular in case of subgingival preparations. The aim of these in vitro study was to evaluate the accuracy among four different IntraOral Scanners (IOSs) in scanning a subgingival vertical margins preparation (VP). A reference maxillary typodont (MT) was fabricated with a VP for full crown on #16 and #21. The MT was scanned with a laboratory scanner (Aadva lab scanner, GC, Tokyo, Japan) to obtain a digital MT (dMT) in .stl format file. A group of 40 digital casts (dIOC) were obtained by scanning the MT 10 times with four different IOSs (Trios 3, 3Shape A/S), ( I700, Medit), (Vivascan, Ivoclar), (Experimental IOS, GC). All the obtained dIOCs were imported into an inspection software program (Geomagic Control X; 3D SYSTEMS) to be superimposed to the dMT, to calculate trueness. Therefore, in order to calculate precision all the scans of the same scanner group were superimposed onto the cast that obtained the best result of trueness. Results were collected as root mean square value (RMS) on #16 and #21 abutment surfaces and on a marginal area positioned 1 mm above and below the gingival margin. A nonparametric analysis Kruskal-Wallis test was performed to compare the RMS values obtained in the different iOS groups for trueness and precision. Statistically significance was set at 0.05. The trueness on #16 abutment, did not statistically differ in between the IOS, while on #21 abutment, Vivascan (56.0 ±12.1) and Experimental IOS, GC (59.2±2.7) performed statistically better than the others. Regarding precision Experimental IOS, GC and Trios 3 were significantly better than I700 and Vivascan both in the #16 (10.7±2,1; 15.8 ± 2,7) and in the #21 area (16.9±13.8 ; 18.0±2.7). At marginal level for both #16 and #21 all the IOS reported reduced accuracy compared to clinical acceptance.

This study was conducted to investigate bit use in equestrian sports, focusing on welfare and performance as bit use has been subject of debate. The multi-faceted study combines a literature review, survey, and video analyses. Research on physiological and behavioral effects of bit use, discussing concerns and benefits, was evaluated. The survey involved 250 equestrians, gathering data on experiences, opinions, and practices regarding bit usage. Results demonstrate that different bits are used during competitions and that riders prioritize factors like horse satisfaction, consistent connection, and chewing behavior when riding at home, while show use focusses on factors like control. Video analyses showed high conformity between veterinary expert and show jumper, indicating reliability and validity. Pelham and loose ring bits were most used, while 3-ring and full cheek bits were associated with the most aversive movements, particularly opening of the mouth. Other defense movements included putting ears back, tail swishing, and head tilting. The study highlighted the need for understanding bit preferences in various settings and cautioned against generalizing bit usage based solely on show observations. It also emphasized the potential for developing new designs that prioritize horse comfort and responsiveness, to enhance communication and partnership between horses and riders.

Precision medicine approaches often relies on complex and integrative analysis of multiple biomarkers from “omics” data to generate insights that can help either diagnostics, prognostics or therapeutical decisions. Such insights are often made using Machine learning (ML) models that make sample classification for a particular phenotype (yes/no). Building such models is a challenge and time-consuming, requiring advanced coding skills and mathematical modelling expertise. Artificial intelligence (AI) is a methodological solution that has the potential to facilitate, optimize and scale model development. In this work, we developed an AI-based, user-friendly and code-free platform (https://digitalphenomics.com) that fully automates the development of predictive models from quantitative “omics” data. Here, we show the application of this tool with the development of cancer survival prognostics models using real-life data from breast, lung and renal cancer transcriptomes. We report and compare their sensitivity, specificity, accuracy and Receiver Operating Characteristic (ROC) curve Area Under the Curve (AUC). Further, we report the associated sets of genes (biomarkers) and their expression pattern that are predictive of cancer survival. Moreover, we made our models available as online tools to generate prognostic predictions based on the gene expression of the biomarkers. In conclusion, we demonstrated that our tool is a robust user-friendly solution to develop bespoke predictive tools from “omics” data which facilitate precision medicine introduction to the point-of-care.

Background: The popularity of climbing via ferratas (VF) in the European Alps has increased a lot. We have analysed the pattern of injuries from accidents, which have occurred on VF, and First Aid (FA) knowledge from the persons on such alpine routes. The aim was to create specific FA courses for those who climb VF. Material and Methods: Incidences and FA knowledge of the alpinists were investigated by a questionnaire. Data included details of the individual’s alpine experience, accidents or any kind of medical emergency they have ever experienced. FA knowledge was evaluated by 18 multiple choice questions with 5 answers each. The questionnaire was based on those of previous studies but was slightly adopted for VF. For this data from rescue operations on VF were used. Finally every participant was asked to judge his FA knowledge by a Likert scale (1 to 5). Results: The collective consisted of 391 participants (28.4% women) with an average age of 41 years. A significant portion did no regular fitness training and in most cases the last FA training was years ago. Nobody had joined a specific FA course for climbers or mountaineers. The most common causes of emergencies were: weather conditions (19%), stumble (18.6%), falls (13.4%), and weariness and deficiency in concentration (13.4%). FA questions most often answered correctly were cardiac emergencies (49.6%), high altitude cerebral edema (HACE) (43.2%), snow blindness (40.9%), injuries of the head (37.1%) and hemorrhagic shock (35.3%). Those most often wrong were injuries of the back (1.0%), injuries of the thorax (2.8%), frostbite (9.0%), acute mountain sickness (AMS) (4.1%) and strategy of rescue (4.1%). VF climbers show significant less FA knowledge than mountaineers in the Western Alps and trekkers. Conclusions: Data support the need of a specific FA training for VF climbers. Their FA knowledge does not fit with the demands in the mountains while some other knowledge they have is negligible on VFs (e.g. HACE). This is in accordance with earlier studies in “classic” alpine mountaineering and in trekking.

Background: Spinal pain is highly prevalent and in Spain it produces a very high economic cost and the scientific evidence supporting treatments shows low to moderate evidence for exercise. Therefore, the aim of this study was to assess the effectiveness of a therapeutic group exercise protocol in reducing pain intensity and disability in patients with spinal pain in primary health care setting. Methods: A total sample of 149 patients who suffered from chronic non-specific spinal pain. Patients received a therapeutic exercise protocol, including exercises of auto-mobilization of the neck and lumbar regions, as well as core stabilization exercises. Pain intensity and disability were evaluated before and after the therapeutic exercise protocol. Results: Statistically significant differences (P&lt;0.05) were shown for pain intensity and disability of patients with neck and low back pain with an effect size from moderate to large. Conclusions: A therapeutic exercise protocol may provide beneficial effects on disability and pain intensity in patients with chronic non-specific spinal pain, including neck and low back pain conditions. Clinicians should consider the use of self-administered exercise protocols, demonstrate great effectiveness, and be less costly.

Obtaining a proper position for THA’s components is a crucial aspect for the implant perfor-mance and consequently patient outcomes. Patient specific kinematic seems to be a key factor to reach the optimal implant positioning. The aim of this study was to assess the accuracy and safety of a computed dynamic analysis system which through patient specific guides tries to improve implant positioning and functional orientation according to patient’s spinopelvic mobility and anatomy.A total of 100 consecutive patients were prospectively enrolled. All patients received an OPS dynamic hip preoperative planning. A TC scan protocol follow up analysis has done at 6 month after surgery.The mean deviation from the planned acetabular inclination and anteversion was 4.3° e 3.8° respectively. The 98% of cases was within +/- 10° of Lewinnek safe zone both for inclination and anterversion. The height of osteotomy deviated on the average of 1.6mm. The 100% cases were included within 4mm of osteotomy. Patient specific and laser guided instru-mentation is safe and accurately reproduce the dynamic planning in terms of components orien-tation, osteotomy level, leg length and offset.

Introduction: Type 2 Diabetes mellitus (T2DM) is a common disease burdened with significant morbidity and mortality. Despite the substantial number of new available drug treatments, adherence to therapy and adverse drug reactions (ADRs) are the major constrain in the management of this disease. We evaluated the use, the adherence and the dsaftey of antidiabetic drugs in patients with T2DM. Methods: we performed an observational, retrospective, multicenter study on medical records of outpatients referred to general practitioners. Drug adherence was measured in agreement to the European Society for Patient Adherence, Compliance and Persistence Medication Adherence Reporting Guideline. ADRs were evaluated using the Naranjo probability scale. Collected data were analyzed using the Statistical Package for the Social Sciences. Results: During the study we evaluated 12,170 medical records of 7 general practitioners. The most prescribed drug was metformin alone (28.4%) or with other oral antidiabetics (19.6%) and then insulin (n: 354; men 190, women 164). Enrolled patients were stratified as high (35%), medium (41%) and low (24%) adherence. Logistic regression showed an association between T2DM less than or equal to 5 years and low adherence (P = 0.023). During the study we recorded 26 ADRs that was correlated with sex (women) and insulin treatment. Conclusion: this real-life study shows that patients with T2DM have high adherence probably related dto a low number of ADRs

: Ovarian cancer has a dismal prognosis. Standard treatment following surgery relies on platinum-based chemotherapy. However, sizeable percentages of patients are unresponsive. Identification of markers predicting response to chemotherapy might help select eligible patients while sparing unresponsive ones treatment-associated toxicity. Cancer/testis antigens (CTA) are expressed by healthy germ cells and malignant cells of diverse histological origin. This expression profile identifies them as attractive targets of cancer immunotherapies. We analyzed correlations between expression of MAGE-A10 and New York esophageal-1 cancer (NY-ESO-1) CTAs at protein level and effectiveness of platinum-based chemotherapy in patients with advanced-stage high-grade serous ovarian carcinoma (HGSOC). MAGE-A10 and NY-ESO-1 protein expression was analyzed by immunohistochemistry (IHC) in formalin-fixed, paraffin-embedded samples from 93 patients with advanced-stage HGSOC treated at our institutions between January 1996 and December 2013. Correlation between expression of these markers and response to platinum-based chemotherapy, evaluated according to RECIST 1.1 criteria, platinum sensitivity, measured as platinum free interval (PFI), progression free (PFS) and overall survival (OS) was explored. MAGE-A10 protein expression predicts unresponsiveness to platinum-based chemotherapy (p=0.005), poor platinum sensitivity (p<0.001), and poor PFS (p<0.001) and OS (p<0.001). Multiva-riate analysis identifies MAGE-A10 protein expression as independent predictor of poor platinum sensitivity (p=0.005) and shorter OS (p<0.001). Instead, no correlation was observed between NY-ESO-1 protein expression and response to platinum-based chemotherapy (p=0.832), platinum sensitivity (p= 0.168), PFS (p=0.126) and OS (p=0.335). MAGE-A10 protein expression reliably identifies advanced-stage HGSOC unresponsive to platinum-based chemotherapy. Targeted im-munotherapy could represent an important alternative therapeutic option in these cancers.

(1) Background: Endoscopic submucosal dissection (ESD) has been widely accepted as the standard method for treating early-stage cancer or precancerous lesions in the upper gastrointestinal tract, however it may be difficult in patients with liver cirrhosis due to coagulation dysfunction or presence of gastroesophageal varices. We aimed to demonstrate the safety and efficacy of ESD in these population. (2) Methods: We retrospectively collected the clinical data and analyzed. Patients inclusion criteria: 1) patients with liver cirrhosis; 2) patients who underwent ESD; 3) patients diagnosed of early-stage cancer or precancerous lesions in the upper gastrointestinal tract. (3) Results: Eight patients were enrolled from April 2019 to April 2023, of whom 3 were male and 5 female, with age ranging from 43 to 70 years old. Seven lesions were located in the stomach, and the other one lesion in the esophagus. ESD was performed successfully in all patients, and the resected lesion size ranged from 2 to 6 cm. Only one patient encountered postoperative complication, chest pain and fever. No recurrence of noticed during a follow-up of 6 to 36 months. (4) Conclusions: ESD is safe and effective for treating upper gastrointestinal early-stage cancer or precancerous lesions in patients with liver cirrhosis.

Unfortunately in recent years, the global healthcare system has noted a notable increase in the prevalence of obesity and its associated health complications. What is more, one of the significant phenomena is the increasing demand for bariatric procedures among individuals of working age. This trend is pronounced in Poland., due to the increasing number of patients meeting the qualifying criteria for surgery among the group of professionally active and as well as unactive patients. The aim of the study is to characterize alarmingly increasing number of candidates for bariatric procedures among professionally active Poles, who underwent occupational medicine examinations in Poland in 2016-2022 and its strong relationship with cardiovascular co-morbidities (POL-O-CARIA 2022 study). In total, the results of 2,056,861 initial, control and periodic visits as part of the occupational medicine certificate were analyzed. Statistical calculations were performed with the use of IBM SPSS Statistics 25. It was noticed that, there was a consistent rise in the proportion of individuals classified as candidates for bariatric procedures ( increase of 0.3%) alongside a notable decrease in the percentage of individuals maintaining a healthy body weight Moreover, it is imperative to conduct yearly evaluations of the prevalence of obesity and its associated health conditions. This proactive approach is essential in order to adequately equip the healthcare system for addressing the increasing population of obese individuals who are actively engaged in their professions. By doing so, we can strategically implement the most efficient interventions to counteract this trend and ensure optimal health outcomes.

Moyamoya disease is also termed a spontaneous obstruction of the arteries in the circle of Willis. It is recognized as the leading cause of ischemic and hemorrhagic stroke. The infrequent cause of stroke is radiologically characterized by the continuous progression of stenosis of the end portion of the bilateral internal carotid artery and compensatory capillaries collaterals. A 1yr old child was admitted to the pediatric I.C.U with a complaint of decreased sensorium, decreased food intake and decreased right upper and lower extremity movements past two days. He had a history of convulsions at seven months of age. He was diagnosed with Moyamoya disease on Magnetic Resonance cerebral angiography. The clinical findings on MR-Angiography show multiple collaterals noted around Circle of Willis, specifically around the posterior communicating artery, anterior communicating artery, posterior cerebral artery, bilateral lenticulostriate, thalamoperforating arteries and medialfrontobasal arteries, which is suggestive of Moyamoya disease. Magnetic resonance imaging of the brain shows Gyral diffusion restriction in a right fronto-parieto-temporal region with mild swelling. The above clinical findings on MR-angiography show the Moyamoya disease in 1year old male child. These clinical findings on MR-Angiography and M.R.I – brain and neck can help the clinician accurately diagnose and manage this rare case.

With enhanced life expectancy and ageing global populations, the prevalence of multimorbidity continues to increase. However, there is a dearth of evidence linked to multimorbidity diagnoses, treatments and health outcomes which remains a concern for future proofing optimal healthcare services. Generating evidence is critical to managing multimorbidity, promoting public health and minimizing health inequalities via effective healthcare policies that improve quality of life for vulnerable populations. This study assessed meta-epidemiology of multimorbidity to report the gaps in scientific knowledge and clinical practice. A systematic methodology was designed and published in PROSPERO (CRD42022347308) to report meta-epidemiology analyses using databases including PubMed, Web of Science, ScienceDirect, EMBASE, The Cochrane Gynaecology and Fertility Group Specialised Register of Controlled Trials and MEDLINE for studies published between the 1^st of January 1980 - 31^st December 2022. A random-effects model was used to estimate the pooled proportion of multimorbidity in adults. Forest plots, pooled odds ratios and statistical heterogeneity metrics were used to assess the association between multimorbidity and investigated factors. Funnel plots and Egger’s regression were used to detect and correct for publication bias. Our findings identified women to be 0.32 times more likely to have multimorbidity in comparison to males. In regard to ethnicity, white people were 0.47 times less likely to develop comorbidities than black people. People who identified as a drinker or unmarried were more likely to develop comorbidities than those who are non-drinkers or married, respectively. Regardless of smoking status, people were equally likely to have comorbidity. In terms of environmental influences, people in rural areas were found to be 0.2 times less likely to have comorbidity in comparison to those living in urban areas. Interestingly, people with a higher education level were 0.57 times more likely to develop comorbidities than those with only a high school education. It is evident that multimorbidity has a significant burden globally and impacts the provision of care necessitated across populations given its association with several social determinants of health. Robust research and healthcare policies are required to better manage multimorbidity in patients. An example of such intervention includes employing prevention programs to reduce risk and incidence of multimorbidity within at-risk populations.

Mucinous breast carcinoma is a rare subtype of mammary neoplasm encountered in medical practice. It represents approximately 1-6% of all breast cancers and is more common in postmenopausal women. There are two subtypes of mucinous breast carcinoma: pure and mixed. We report the case of a 73-year-old Caucasian woman diagnosed with mucinous pancreatic cystadenoma in 2007. She underwent a surgical procedure involving pancreatectomy of the body and tail, along with multiple known cardiovascular and metabolic comorbidities. In November 2019, during a clinical-biological evaluation for associated diseases, a mucinous carcinoma of the right breast was accidentally detected and later confirmed through further investigations. For treatment, a surgical procedure was performed involving lower right quadrantectomy with right axillary lymph node dissection. The postoperative clinical course was favorable. In conclusion, we present the case of a patient diagnosed with mixed mucinous breast carcinoma, without axillary lymph node invasion. Postmenopausal women with diabetes, overweight, and obesity have an increased susceptibility to breast cancer, with our patient having all these risk factors. To date, no study has demonstrated the genetic or radiation implication in the occurrence of mucinous carcinomas, nor the possible development of mucinous carcinomas in series in the same patient. Current data are insufficient to provide recommendations for the screening of malignant mucinous tumors in subjects with significant cardiometabolic risk factors.

Lung cancer accounts for the majority of cancer cases. In recent years, checkpoint inhibitor immunotherapy (ICI) has emerged as a new treatment. A better understanding of the tumor microenvironment, or TMJ, or the immune system surrounding the tumor is needed. Cytokines are small proteins that carry messages between cells and are known to play an important role in the body's response to inflammation and infection. Cytokines are important for immunity in lung cancer. It promotes tumor growth (oncogenic cytokines) or inhibits tumor growth (anti-tumor cytokines) by controlling signaling pathways for growth, proliferation, metastasis, and apoptosis. The immune system relies heavily on cytokines. They can also be produced in the laboratory for therapeutic use. Cytokine therapy helps the immune system stop the growth or kill cancer cells. Interleukins and interferons are two types of cytokines used to treat cancer. This article begins by addressing the role of the tumor microenvironment (TMJ) and its components in lung cancer. This review also highlights the functions of various cytokines such as IL, TGF and TNF.

Dilated cardiomyopathy (DCM) is a common form of cardiomyopathy, characterized by ventricular chamber dilatation and systolic dysfunction, in the absence of coronary artery disease, arterial hypertension, valvular or congenital diseases. DCM is a heterogeneous group of disorders of the myocardium caused by genetic factors, environmental factors, or a combination of both. DCM affects mainly men aged between 20 and 50 years, being considered one of the main causes of heart failure (HF) and the main indication for heart transplantation. Guideline-based HF treatment is the mainstay of management for patients with DCM. In recent years, gene therapy and induced pluripotent stem cells have become promising strategies. In this review, we summarize the relevant clinical issues, and current treatment of DCM patients, including the role of genetic evaluation.

Serum albumin (ALB), one of the most important proteins in human physiology, has the main functions of maintaining plasma oncotic pressure and plasma volume, transporting hormones, vitamins, oligominerals and drugs, and exerting a powerful antioxidant-antiinflammatory role. Its prognostic value in liver and malabsorption syndromes is well known. In this narrative review, an analysis of the most important studies evaluating the prognostic significance of low serum ALB levels in hospitalized patients was performed. Specifically, the risk in emergency medicine, cardiovascular diseases, COVID-19 infection, nephrology, oncology and autoimmune rheumatic diseases has been examined to fully explore its clinical value. ALB is a negative acute-phase reactant and the reduction of its serum levels represents a threatening parameter for long-term survival in several clinical settings, and a strong poor prognostic biomarker in most diseases. Therefore, clinicians should consider serum ALB as a valuable tool to assess the efficacy of specific therapies, both in hospitalized patients and in chronic follow-up.

Atrial fibrillation (AF) is a common arrhythmia associated with various risk factors and significant morbidity and mortality. This article presents findings from a study involving 115 patients with permanent AF. The study examined demographics, risk factors, associated pathologies, complications, and anticoagulant therapy. The results showed a slight predominance of AF in males, with the highest incidence in individuals aged 75 and above. Common risk factors included arterial hypertension, dyslipidaemia, diabetes mellitus type 2, and obesity. Comorbidities such as congestive heart failure, mitral valve regurgitation, and pulmonary disorders were prevalent among the patients. Major complications included congestive heart failure, stroke, and myocardial infarction. Thromboembolic and bleeding risk assessment using CHAD2DS2-VASc and HAS-BLED scores demonstrated a high thromboembolic risk in all patients. The majority of patients were receiving novel oral anticoagulants (NOACs) before admission, while NOACs were also the most prescribed antithrombotic therapy at discharge. The study highlights the importance of risk factor management and appropriate anticoagulant therapy in AF patients to reduce complications and improve outcomes.

Vaccines are an important tool of preventive medicine. Organized vaccination programs have saved numerous people from serious infectious diseases. Surprisingly, there is a considerable portion of the population who oppose vaccinations. In particular, the existence of anti-vaccination perceptions among travelers to countries with endemic diseases is a major public health concern. Although hesitancy towards vaccinations is not a novel phenomenon, it came back to the forefront during the fight against the COVID-19 pandemic. This review explored the etiology of anti-vaccination beliefs among travelers and drew conclusions about their impact on public health and society in general. For this purpose, a purposeful search for data on the causative factors of vaccine hesitancy and their impact on people’s health was conducted. A descriptive analysis of the findings and conclusions about possible implications in health policy and clinical practice are presented. Fear of side effects, lack of credence in the necessity of vaccines, and mistrust of medical authorities are important causative factors. Their interplay shapes hesitancy towards vaccines. However, anti-vaccination beliefs can also be an aspect of a more general unconventional stance of life. Health care professionals and organizations must be ready to tackle vaccine hesitancy by making the necessary interventions. Correcting misconceptions about vaccinations is a prerequisite for ensuring personal and public health, especially in the context of a pandemic or epidemic. Moreover, ensuring the efficacy and safety of vaccines, especially in cases of modern technology applications, is a fundamental factor in addressing people’s concerns about vaccines. For this purpose, medical authorities and organizations must provide accurate and clear information on vaccines so as to eliminate misinformation. Furthermore, clinicians should cultivate their communication skills in order to convey the appropriate messages to prospective recipients of vaccinations.

Atherogenic lipoproteins may impair vascular reactivity, leading to tissue damage in various organs, including the eye. This study aimed to investigate whether ophthalmic artery reactivity is affected in mice lacking the apolipoprotein E gene (ApoE-/-), a model for hypercholesterolemia and atherosclerosis. Twelve-month-old male ApoE-/- mice and age-matched wild-type controls were used to assess vascular reactivity using videomicroscopy. Moreover, vascular mechanics, lipid content, levels of reactive oxygen species (ROS), expression of pro-oxidant redox enzymes and of the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) were determined in vascular tissue. Unlike the aorta, the ophthalmic artery of ApoE-/- mice developed no signs of endothelial dysfunction and no signs of excessive lipid deposition. Remarkably, levels of ROS, nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1), NOX2, NOX4, and of LOX-1 were increased in the aorta but not in the ophthalmic artery of ApoE-/- mice. Our findings suggest that ApoE-/- mice develop endothelial dysfunction in the aorta by increased oxidative stress via involvement of LOX-1, NOX1 and NOX2, whereas NOX4 may participate in media remodeling. In contrast, the ophthalmic artery appears to be resistant to chronic apolipoprotein E deficiency. Lack of LOX-1 expression/overexpression in response to increased ox-LDL levels may be a possible mechanism of action.

Abstract: Autism spectrum disorders (ASDs) are complex, lifelong, neurodevelopmental conditions of largely unknown cause. The global prevalence of autism has increased twentyfold to thirtyfold since the earliest epidemiologic studies were conducted in the late 1960s and early 1970s. Recent reports agree on the association of ASD with the alteration of the microbiome (dysbiosis), which raises the possible role of external factors. Our study aimed at identifying antibiotic classes that might be associated with the development of ASD-related dysbiosis either promoting or inhibiting the process. Statistical comparison was made between the average yearly consumption of different antibiotic classes (1997-2020) and the number of individuals living with ASD estimated for 2023/100000 population in 30 European countries and the results were statistically analyzed. Tetracycline (J01A) showed significant positive (promoting) association with the prevalence of ASD (Pearson r: 0.373, p: 0.043. OR: 1.312, CI95%: 0.995-1.791, p: 0.065) and narrow-spectrum, beta-lactamase resistant penicillin (J01CF) (Pearson r: 0.524, p: 0.003, OR: 3.240, CI95%: 1.710-8.853, p: 0.004, Kruskal-Wallis p: 0.032). Mild, negative (inhibitory) association was observed with broad-spectrum, beta-lactamase sensitive penicillin (J01CA) (Pearson r: -0.278, p: 0.157, OR: 0.808, CI95%: 0649-0957, p: 0.028) and narrow-spectrum, beta-lactamase-sensitive penicillin (J01CE) (Pearson p: -0.032, r: 0.865, OR: 0.725, CI95%: 0.543-0.885, p: 0,009). Our findings strongly support the animal experiments when penicillin-exposed newborn mice developed "autism-like" behavior.

Introduction and Objective: Caudal block has been used in children for many years and is considered the gold standard for multimodal analgesia in the pediatric age group. Caudal block belongs to the category of central neuraxial blocks, which can provide both visceral and somatic analgesia. With the introduction of ultrasound into the clinical practice of anaesthesia, the caudal block is now performed under USG guidance. In our study, we aimed to compare the efficacy of a single caudal block in postoperative acute pain management, the need for additional analgesics, the incidence of side effects, the timing of initial analgesic administration, and the need for rescue analgesic administration (paracetamol 10 mg/kg) in circumcision surgery. Materials and Methods: 120 patients undergoing circumcision surgery were divided into 3 groups. The caudal block was performed in all cases under USG guidance. Only the caudal block was applied for cases in the Caudal group (Group C). The Caudal + paracetamol group (Group CP) received paracetamol 10 mg/kg intravenously (i.v.) and the caudal block. Patients in the Caudal + meperidine group (Group CM) received 1 mg/kg meperidine intravenously. The caudal block was performed in each case with a 0.5 ml/kg volume of 0.125% bupivacaine. Results: As a result of our study, it was found that the least postoperative pain occurred in 12.50% of the CM group (p=0.011). Significant results were obtained when weight and age variables were analyzed according to the groups (p-values p=0.011 and p=0.003, respectively). Significant differences were found between the input pulse values, 5-minute pulse values, 15-minute pulse values, and input SpO2 values (p values p < 0.001, p < 0.001, p=0.011, p=0.037, respectively). Only Wong-Baker pain scores at the 24th hour differed significantly from the periods measured after the groups (p < 0.001). There was no significant difference between the FLACC and Wong-Baker pain scores in the other periods. There was no difference between the groups regarding the time when postoperative analgesics were administered and the total amount of analgesics administered (rescue analgesic 10 mg/kg oral paracetamol) (p=0.408, p=0.238). Conclusion: Caudal block can be safely applied during circumcision. Ultrasound guidance increases the chances of success and reduces the complication rate. Caudal block can be safely used in pediatric surgery since it does not cause serious complications, has low postoperative pain scores, and reduces the number of postoperative analgesics.

Fabry disease (FD) is a recessive monogenic inheritance disease linked to chromosome X, secondary to mutations in the GLA gene. Its prevalence is estimated between 1:8,454 and 1:117,000 among males and is probably underdiagnosed. Mutations in the GLA gene lead to the progressive accumulation of globotriaosylceramide (Gb3). Gb3 accumulates in lysosomes of different types of cells of the heart, kidneys, skin, eyes, central nervous system, and gastrointestinal system, and may lead to different clinical scenarios. The impairment of the nervous system, in addition to the acroparesthesias, is characterized by hypohidrosis and cerebrovascular accidents. Gb3-accumulation supports the hypothesis that Gb3 is not solely responsible for disease manifestation. Overloading of lysosomes with Gb3 may simply lead to the rupture of cytoplasma and in consequence to cell death .Secondary effects of Gb3 accumulation which might be responsible for disease pathology include also inflammatory processes. Perturbed leukocyte function in Fabry disease compared to healthy controls and abnormal numbers of different immune cells, including lymphocytes, monocytes, CD8+ cells, B cells and dendritic cells . Noteworthy other studies reported no correlation between CRP-levels as a global inflammatory marker and the Mainz-Severity-Score-Index (MSSI) as a marker for disease severity . Other authors reported on auto-immunological reactions in α-galactosidase A deficiency. Others researchers found higher expressions of neuronal apoptosis inhibiting protein as a key anti-apoptotic mediator in children with Fabry disease compared to healthy controls. Noteworthy, this upregulation did not change after institution of ERT, whereas apoptosis inducing factor appears to be upregulated under ERT. The authors were not able to explain their observations, but further research has to be directed on this topic. Gb3-accumulation has been reported to induce oxidative stress and/or the formation reactive oxygen species (ROS). Lipids and proteins may be oxidised and may be unable to function. Of note, ERT increased the generation of ROS in vitro, and up-regulated the intracellular adhesion molecule ICAM 1. The authors hypothesized that ERT may enhance endothelial damage, allowing to understand continuously occurring strokes in patients on treatment. Furthermore, Gb3-accumulation has been reported to induce oxidative stress and/or the formation reactive oxygen species (ROS). Lipids and proteins may be oxidised and may be unable to function. Of note, ERT increased the generation of ROS in vitro, and up-regulated the intracellular adhesion molecule ICAM 1. Another gateway into alteration of endothelial function may be given by the Nitric-Oxide-Synthase-3-genotypes. Endothelium-derived nitric oxide is a key regulator of vessel wall function and cardiovascular homeostasis. Thus, neurological complications seem to be linked to different pathogenetic molecular mechanisms.Progressive accumulation of GB3 represent a possible pathogenetic event of peripheral nerve involvement, whereas central nervous involvement in the clinical setting of cerebrovascular ischemic events seem to be due to the endotheliopathy of Anderson-Fabry Disease with lacunar lesions and white matter hyperintensities ( WMHs) . In this review manuscript we revised molecular mechanisms of peripheral and central neurological complications of Anderson-Fabry Disease.

Testosterone (T), the principal androgen secreted by the testes, plays an essential role in male health. Male hypogonadism is diagnosed based on a combination of associated clinical signs and symptoms and laboratory confirmation of low circulating T levels. In this review we have highlighted factors, both biological and analytical, that introduce variation into the measurement of serum T concentrations in men; these need to be considered when requesting T levels and interpreting results. There is an ongoing need for analytical standardisation of T assays and harmonisation of pre- and post-analytical laboratory practices, particularly in relation to the laboratory reference intervals provided to clinicians. Further, there is a need to share with service users the most up-to-date and evidence-based action thresholds for serum T as recommended in the literature. Estimation of free testosterone may be helpful. Causes of secondary hypogonadism should be considered. A comprehensive approach is required in the management of male hypogonadism, including lifestyle modification, as well as medication where appropriate. The goal of treatment is resolution of symptoms as well as optimisation of metabolic, cardiovascular and bone health. The advice of an endocrinologist should be sought, where there is doubt about the cause and appropriate management of the hypogonadism.

We report two cases of pancytopenia in patients after recovering from a mild COVID-19, now presenting as paroxysmal nocturnal hemoglobinuria (PNH) and aplastic anemia. These cases il-lustrate a common pathway whereby a viral trigger causes clonal expansion of a hematological disorder. Although the association in both cases are temporal, and that COVID-19 may be an in-cidental diagnosis, the growing evidence related to hematological effects of SARS-CoV-2 infec-tion highlights the need for further investigation into the hematological consequences of COVID-19, particularly in the post-pandemic era.

Sepsis-associated encephalopathy (SAE) is a common brain dysfunction following sepsis that often results in severe cognitive and neurological sequelae and increases the mortality rate in patients with sepsis. Microglia are resident macrophages in the brain that play essential roles in the pathological and physiological processes of SAE. Depending on the nature of the stimulus, microglia can adopt two polarization states (M1/M2), which correspond to altered microglial morphology, gene expression, and function. Therefore, we systematically described the pathogenesis, morphology, function, and phenotype of microglial activation in SAE. We demonstrated that microglia are closely related to occurrence and development of SAE and concomitant cognitive impairement. Finally, we outlined some potential therapeutic approaches that can prime microglia and neuroinflammation towards the beneficial restorative microglial phenotype in SAE.

Idiopathic acute pancreatitis (IAP) presents a diagnostic challenge and refers to cases where the cause of acute pancreatitis remains uncertain despite a comprehensive diagnostic evalua-tion. Endoscopic ultrasound (EUS) has emerged as a valuable tool in the diagnostic workup of IAP. This review explores the pivotal role of EUS in detecting the actual cause of IAP, as-sessing its accuracy, timing, safety, and future technological improvement. Following PRISMA guidelines, 60 pertinent studies were selected and analysed. EUS emerges as a cru-cial diagnostic tool, particularly when conventional imaging fails. It can offer intricate visu-alization of the pancreas, biliary system, and adjacent structures. High accuracy of EUS is evident in detecting the actual causes of IAP such as microlithiasis, small bile duct stones, pancreas divisum, and small pancreatic tumors. Optimal timing for EUS is post-resolution of the acute phase of the disease. EUS, when conducted by experienced endoscopists, it boasts minimal safety concerns, and is crucial to prevent complications. EUS-guided interventions, including fine-needle aspiration, collection drainage, and biopsies, aid in cytological analy-sis. With high diagnostic accuracy, safety, and therapeutic potential, EUS is able to improve patient outcomes when managing IAP. Further refinement of EUS techniques and cost-effectiveness assessment of EUS-guided approaches need to be explored in multicenter prospective studies. This review underscores EUS as a transformative tool in unraveling IAP's enigma and advancing diagnostic and therapeutic strategies.

Background & Aims: Gut microbial imbalances are linked to colorectal cancer (CRC), but archae-‎a's role remains underexplored. Here, we performed bioinformatic and statistical analysis looking ‎for archaeal taxonomic and functional signatures related to CRC. Methods: We analyzed pub-‎lished fecal metagenomic data from 390 subjects, comparing the archaeomes of CRC and healthy ‎individuals. We conducted a biostatistical analysis to investigate the relationship between Candi-‎datus Mancarchaeum acidiphilum (DPANN superphylum) and other archaeal species associated ‎with CRC. Using the Prokka tool, we annotated the data focusing on archaeal genes, subsequently ‎linking them to CRC and mapping them against UniprotKB and GO databases for specific ar-‎chaeal gene functions. Results: Our analysis identified enrichment of methanogenic archaea in ‎healthy subjects, with an exception for Methanobrevibacter smithii, which correlated with CRC. ‎Notably, CRC showed a strong association with archaeal species, particularly Natrinema sp. J7-2, ‎Ferroglobus placidus, and Candidatus Mancarchaeum acidiphilum. Furthermore, the DPANN ar-‎chaeon exhibited a significant correlation with other CRC-associated archaea (p < 0.001). Func-‎tionally, we found a marked association between MvhB-type polyferredoxin and colorectal can-‎cer. We also highlighted the association of archaeal proteins involved in the biosynthesis of leucine ‎and the galactose metabolism process with the healthy phenotype. Conclusion: The archaeomes ‎of CRC patients show identifiable alterations, including a decline in methanogens and an increase ‎in Halobacteria species. MvhB-type polyferredoxin, linked with CRC and species like Candidatus ‎Mancarchaeum acidiphilum, Natrinema sp. J7-2 and Ferroglobus placidus emerge as potential archaeal ‎biomarkers. Archaeal proteins may also offer gut protection, underscoring archaea’s role in CRC ‎dynamics.

This study aimed to translate and psychometrically validate the Neck Outcome Score (NOOS) in the Polish population according to the recommendations of American Academy of Orthopedic Surgeons (AAOS) for the Cross-Cultural Adaptation of Health Status Measures. Participants completed the NOOS, Neck Disability Index (NDI), and Visual Analogue Scale (VAS) for pain assessment. The questionnaires were completed by 57 women and 32 men with cervical spine ailments. A retest was performed in all patients after 48 hours. The analysis confirmed the high internal consistency (Cronbach's alpha of 0.95) of the Polish NOOS. No floor / ceiling effects were observed. The Polish NOOS showed a significant correlation with NDI (0.87; p<0.001) and VAS (0.79; p<0.001). The intraclass correlation coefficient (ICC) for the test-retest was found to be high (0.97). The Polish version of NOOS can be used for clinical and research purposes as an equivalent to the original English version. This study contributes to the area of patient-reported outcome measures available in the Polish language.

Glioblastoma (GBM) is an aggressive and lethal primary brain tumor with restricted treatment options and a dismal prognosis. Oncolytic virotherapy (OV) has developed as a promising approach for GBM treatment. However, reaching invasive GBM cells may be hindered by tumor-surrounding, non-neoplastic cells when the OV is applied intratumorally. In this study, using a rodent GBM model and immunofluorescence analyses, we investigated the intranasal delivery of the oncolytic adenovirus (OAV) XVir-N-31 via virus-loaded, optimized shuttle cells. Intranasal administration (INA) was selected due to its non-invasive nature and the potential to bypass the blood-brain barrier (BBB). Our findings demonstrate that INA of XVir-N-31 loaded shuttle cells successfully delivers OAVs to the core tumor and invasive GBM cells, significantly prolongs the survival of GBM bearing mice, induces immunogenic cell death and finally reduces tumor burden, all this highlighting the therapeutic potential of this innovative approach. Overall, this study provides compelling evidence for the effectiveness of INA of XVir-N-31 via shuttle cells as a promising therapeutic strategy for GBM. The non-invasive nature of INA of OV-loaded shuttle cells holds great promise for future clinical translation. However, further research is required to assess the efficacy of this approach to ultimately progress in human clinical trials.

(1) Background: Vitamin K deficiency is a common feature of chronic kidney disease (CKD), leading to impaired bone quality and increased risk of vascular calcifications. A method to indirectly measure Vitamin K status is measuring the blood level of Vitamin K dependent proteins (VKDP)- osteocalcin (OC) and matrix GLA protein (MGP). The aim of this study is to correlate the level of OC and MGP with markers of CKD mineral bone disorder (CKD-MBD). (2) Methods: We conducted a single-center cross-sectional study that included 45 CKD G5D patients and measured blood biochemistry, complete blood count and intact osteocalcin and matrix GLA protein. (3) Results: We found a strong statistically significant correlation of OC with the markers of CKD-MBD such as: iPTH , serum calcium and serum phosphorus and a strong indirect statistically significant correlation with abdominal circumference. There was also a statistically significant correlation of MGP with markers of inflammation (CRP). Higher levels of MGP were found in patients treated with vitamin K antagonists, non-calcium based phosphate binders and vitamin D receptor activator- paricalcitol. (4) Conclusions: In our study, we found that vitamin K deficiency, measured indirectly using the level of VKDP is associated to CKD-MBD. The use of medication such as phosphate binders, that reduce vitamin K absorbtion, Vitamin D that increases Vitamin K requirements and also vitamin K antagonists, seem to have an influence on the blood level of VKDPs.

Background: The interruption of the activity of the population-based organized colorectal cancer (CRC) screening programs due to the COVID pandemic may have affected their results in terms of detection of preneoplastic lesions and CRC. We evaluated the impact of the COVID pandemic on the delays, participation, adherence to colonoscopies, lesions detected, and CRC stage at di-agnosis in a CRC screening program. Methods: We analyzed all the invitations between January 1, 2019, and December 31, 2021. We defined the pandemic period as the period after March 12, 2020. We calculated the delay intervals (successive and all rounds), the rates of participation, adherence to colonoscopy after a positive fecal immunochemical test (FIT), and the diagnostic yield of colonoscopy, specifically CRC and colorectal neoplasia (CRC and/or adenoma), as well as CRC stage at diagnosis. Results: In the period analyzed, 976,187 invitations were sent (61.0% pandemic), 439,687 FIT were returned (62.4% pandemic) and 23,092 colonoscopies were performed (59.1% pandemic). Colon-oscopies were normal in 7,378 subjects (32.4%) and a CRC was detected in 916 subjects (4.0%). In successive rounds, the delay increased significantly seven months during the pandemic period (p<0.001). In all the invitations, the delay from the invitation to the colonoscopy increased sig-nificantly by 8 days (p<0.001). Once adjusted for the confounding variables, participation in the screening program increased significantly (OR=1.1; 95% CI=1.09-1.11), with no changes in the adherence to colonoscopy (OR=0.9; 95% CI=0.8-1.0). We found no differences in the diagnostic yield of colonoscopy in terms of CRC (OR=0.90; 95% CI=0.78-1.02) or colorectal neoplasia (OR=0.98; 95% CI=0.92-1.03) detection. Finally, we found no differences in CRC stage at diagnosis (p=0.2). Conclusions: Although the interruption of the CRC screening program due to the COVID pan-demic increased the delays, it did not reduce participation, adherence to colonoscopy, or the di-agnostic yield of colonoscopy.

According to cancer death rates for women worldwide, this form of cancer ranks fourth after breast, bronchopulmonary, and colorectal cancer, affecting around 570,000 women annually. About 270,000 women each year pass away from this illness, 85% of them are from underdeveloped nations where cervical cancer claims more lives than any other kind of cancer. In Romania, cervical cancer ranks fourth in terms of death, behind breast, bronchopulmonary, and colorectal cancers, and second in terms of incidence, behind breast cancer. Endometriosis in the cervical region is quite uncommon. Only a tiny fraction of women had the condition upon diagnosis. It might be challenging to detect cervical endometriosis since it rarely manifests any symptoms or markers. Women who are asymptomatic can manage the condition expectantly; however, if the symptoms return often, surgery may be required. As many patients have concurrent diseases such fibroids, adenomyosis, ovarian cysts, and pelvic endometriosis, cervical endometriosis therapy appears to be straightforward. There ought to be surgical intervention. Symptomatic cervical endometriosis, such as irregular or post-coital bleeding, may be treated surgically using the LLETZ surgery or another cervical ablation approach. Background and Objectives: (1) To assess one's degree of knowledge on the signs, causes, and methods of preventing cervical cancer or cervical endometriosis, as well as screening for these conditions. (2) To ascertain how the responder behaves about cervical cancer screening and prevention, as well as endometriosis in the cervical region. Materials and Methods: A case report about cervical cancer or cervical endometriosis was conducted among a patient from Romania, Timisoara. Results: In this study, we report the patient with cervical endometriosis, although he was initially diagnosed with cervical cancer. Conclusions: Cervical cancer, a condition that can have serious repercussions on the patient's health, even if there is no clear picture of paraclinical investigations, to raise the suspicion of cervical endometriosis and not cervical cancer.