Tracheostomy-related data from an intensive care unit for two consecutive years before the COVID-19 pandemic.

BACKGROUND: Tracheostomy is commonly used in intensive care unit (ICU) patients who are expected to be on long-term mechanical ventilation or suffer from emergency upper airway obstruction. However, some studies have conflicting findings regarding the optimal technique and its timing and benefits. AIM: To provide evidence of practice, characteristics, and outcome concerning tracheostomy in an ICU of a tertiary care hospital. METHODS: This was a retrospective cohort study including adult critical care patients in a single ICU for two consecutive years. Patients' demographic characteristics, severity of illness (APACHE II score), level of consciousness [Glasgow Coma Scale (GCS)], comorbidities, timing and type of tracheostomy procedure performed and outcome were recorded. We defined late as tracheostomy placement after 8 days or no tracheotomy. RESULTS: Data of 660 patients were analyzed (median age of 60 years), median APACHE II score of 19 and median GCS score of 12 at admission. Tracheostomy was performed in 115 patients, of whom 63 had early and 52 late procedures. Early tracheostomy was mainly executed in case of altered level of consciousness and severe critical illness polyneuromyopathy, however there were no significant statistical results (47.6% vs 36.5%, P = 0.23) and (23.8% vs 19.2%, P = 0.55) respectively. Regarding the method selected, early surgical tracheostomy (ST) was conducted in patients with maxillofacial injuries (50.0% vs 0.0%, P = 0.033), whereas late surgical tracheostomy was selected for patients with goiter (44.4% vs 0.0% P = 0.033). Patients with early tracheostomy spent significantly fewer days on mechanical ventilation (15.3 ± 8.5 vs 22.8 ± 9.6, P < 0.001) and in ICU in general (18.8 ± 9.1 vs 25.4 ± 11.5, P < 0.001). Percutaneous dilatation tracheostomy (PDT) vs ST was preferable in older critical care patients in the case of Central Nervous System underlying cause of admission (62.5% vs 26.3%, P = 0.004). ST was the method of choice in compromised airway (31.6%, vs 7.3% P = 0.008). A large proportion of patients (88/115) with tracheostomy managed to wean from mechanical ventilation and were transferred out of the ICU (100% vs 17.4%, P < 0.001). CONCLUSION: PDT was performed more frequently in our cohort. This technique did not affect mechanical ventilation days, ventilator-associated pneumonia (VAP), ICU length of stay, or survival. No complications were observed in the percutaneous or surgical tracheostomy groups. Patients undergoing early tracheostomy benefited in terms of mechanical ventilation days and ICU length of stay but not of discharge status, presence of VAP, or survival.

Amyloid beta is associated with carotid wall echolucency and atherosclerotic plaque composition.

Circulating amyloid-beta 1-40 (Αb40) has pro-atherogenic properties and could serve as a biomarker in atherosclerotic cardiovascular disease (ASCVD). However, the association of Ab40 levels with morphological characteristics reflecting atherosclerotic plaque echolucency and composition is not available. Carotid atherosclerosis was assessed in consecutively recruited individuals without ASCVD (n = 342) by ultrasonography. The primary endpoint was grey scale median (GSM) of intima-media complex (IMC) and plaques, analysed using dedicated software. Vascular markers were assessed at two time-points (median follow-up 35.5 months). In n = 56 patients undergoing carotid endarterectomy, histological plaque features were analysed. Plasma Αb40 levels were measured at baseline. Ab40 was associated with lower IMC GSM and plaque GSM and higher plaque area at baseline after multivariable adjustment. Increased Ab40 levels were also longitudinally associated with decreasing or persistently low IMC and plaque GSM after multivariable adjustment (p < 0.05). In the histological analysis, Ab40 levels were associated with lower incidence of calcified plaques and plaques without high-risk features. Ab40 levels are associated with ultrasonographic and histological markers of carotid wall composition both in the non-stenotic arterial wall and in severely stenotic plaques. These findings support experimental evidence linking Ab40 with plaque vulnerability, possibly mediating its established association with major adverse cardiovascular events.

Investigation of Antihypertensive Properties of Chios Mastic via Monitoring microRNA-21 Expression Levels in the Plasma of Well-Controlled Hypertensive Patients.

Hypertension is a chronic, multifactorial disease, leading to high cardiovascular morbidity and mortality globally. Despite the advantages of pharmaceutical treatments, natural products have gained scientific interest due to their emerging phytotherapeutic properties. Chios mastic is a natural Greek product, consisting of bioactive compounds which modify microRNAs' (small, expression-regulating molecules) expression. In this study, we investigated the antihypertensive properties of Chios mastic through the assessment of miR-21 levels. Herein, plasma samples of 57 individuals with hypertension, recruited for the purposes of the HYPER-MASTIC study, were analyzed. This was a clinical trial with Chios mastic supplements in which the patients were divided into groups receiving high and low mastic doses and placebo supplements, respectively. miR-21 was significantly upregulated in patients compared to normotensive individuals. Mean changes in miR-21 levels were statistically significant, after adjusting for sex and age, between the placebo and low-dose group and between the low- and high-dose group. Post-intervention miR-21 levels were positively associated with night-time systolic blood pressure, pulse pressure, and central systolic mean arterial pressure and negatively associated with night-time pulse wave velocity in the low-dose group. Our findings suggest a potential implication of miR-21 in the association of Chios mastic with night-time blood pressure measurements.

Knockout Genes in Bowel Anastomoses: A Systematic Review of Literature Outcomes.

BACKGROUND: The intestinal wound healing process is a complex event of three overlapping phases: exudative, proliferative, and remodeling. Although some mechanisms have been extensively described, the intestinal healing process is still not fully understood. There are some similarities but also some differences compared to other tissues. The aim of this systematic review was to summarize all studies with knockout (KO) experimental models in bowel anastomoses, underline any recent knowledge, and clarify further the cellular and molecular mechanisms of the intestinal healing process. A systematic review protocol was performed. MATERIALS AND METHODS: Medline, EMBASE, and Scopus were comprehensively searched. RESULTS: a total of eight studies were included. The silenced genes included interleukin-10, the four-and-one-half LIM domain-containing protein 2 (FHL2), cyclooxygenase-2 (COX-2), annexin A1 (ANXA-1), thrombin-activatable fibrinolysis inhibitor (TAFI), and heparin-binding epidermal growth factor (HB-EGF) gene. Surgically, an end-to-end bowel anastomosis was performed in the majority of the studies. Increased inflammatory cell infiltration in the anastomotic site was found in IL-10-, annexin-A1-, and TAFI-deficient mice compared to controls. COX-1 deficiency showed decreased angiogenesis at the anastomotic site. Administration of prostaglandin E2 in COX-2-deficient mice partially improved anastomotic leak rates, while treatment of ANXA1 KO mice with Ac2-26 nanoparticles reduced colitis activity and increased weight recovery following surgery. CONCLUSIONS: our findings provide new insights into improving intestinal wound healing by amplifying the aforementioned genes using appropriate gene therapies. Further research is required to clarify further the cellular and micromolecular mechanisms of intestinal healing.

Exploring the DNA Methylation Profile of Genes Associated with Bladder Cancer in Bladder Tissue of Patients with Neurogenic Lower Urinary Tract Dysfunction.

DNA methylation is an epigenetic process that commonly occurs in genes' promoters and results in the transcriptional silencing of genes. DNA methylation is a frequent event in bladder cancer, participating in tumor initiation and progression. Bladder cancer is a major health issue in patients suffering from neurogenic lower urinary tract dysfunction (NLUTD), although the pathogenetic mechanisms of the disease remain unclear. In this population, bladder cancer is characterized by aggressive histopathology, advanced stage during diagnosis, and high mortality rates. To assess the DNA methylation profiles of five genes' promoters previously known to be associated with bladder cancer in bladder tissue of NLUTD patients, we conducted a prospective study recruiting NLUTD patients from the neuro-urology unit of a public teaching hospital. Cystoscopy combined with biopsy for bladder cancer screening was performed in all patients following written informed consent being obtained. Quantitative methylation-specific PCR was used to determine the methylation status of RASSF1, RARß, DAPK, hTERT, and APC genes' promoters in bladder tissue samples. Twenty-four patients suffering from mixed NLUTD etiology for a median duration of 10 (IQR: 12) years were recruited in this study. DNA hypermethylation was detected in at least one gene of the panel in all tissue samples. RAR-ß was hypermethylated in 91.7% samples, RASSF and DAPK were hypermethylated in 83.3% samples, APC 37.5% samples, and TERT in none of the tissue samples. In 45.8% of the samples, three genes of the panel were hypermethylated, in 29.2% four genes were hypermethylated, and in 16.7% and in 8.3% of the samples, two and one gene were hypermethylated, respectively. The number of hypermethylated genes of the panel was significantly associated with recurrent UTIs (p = 0.0048). No other significant association was found between DNA hypermethylation or the number of hypermethylated genes and the clinical characteristics of the patients. Histopathological findings were normal in 8.3% of patients, while chronic inflammation was found in 83.3% of patients and squamous cell metaplasia in 16.7% of patients. In this study, we observed high rates of DNA hypermethylation of genes associated with bladder cancer in NLUTD patients, suggesting an epigenetic field effect and possible risk of bladder cancer development. Recurrent UTIs seem to be associated with increased DNA hypermethylation. Further research is needed to evaluate the impact of recurrent UTIs and chronic inflammation in DNA hypermethylation and bladder cancer etiopathogenesis in NLUTD patients.

Carbon Nanotube-Mediated Delivery of PTEN Variants: In Vitro Antitumor Activity in Breast Cancer Cells.

Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a crucial tumor suppressor protein with frequent mutations and alterations. Although protein therapeutics are already integral to numerous medical fields, their potential remains nascent. This study aimed to investigate the impact of stable, unphosphorylated recombinant human full-length PTEN and its truncated variants, regarding their tumor suppression activity with multiwalled-carbon nanotubes (MW-CNTs) as vehicles for their delivery in breast cancer cells (T-47D, ZR-75-1, and MCF-7). The cloning, overexpression, and purification of PTEN variants were achieved from E. coli, followed by successful binding to CNTs. Cell incubation with protein-functionalized CNTs revealed that the full-length PTEN-CNTs significantly inhibited cancer cell growth and stimulated apoptosis in ZR-75-1 and MCF-7 cells, while truncated PTEN fragments on CNTs had a lesser effect. The N-terminal fragment, despite possessing the active site, did not have the same effect as the full length PTEN, emphasizing the necessity of interaction with the C2 domain in the C-terminal tail. Our findings highlight the efficacy of full-length PTEN in inhibiting cancer growth and inducing apoptosis through the alteration of the expression levels of key apoptotic markers. In addition, the utilization of carbon nanotubes as a potent PTEN protein delivery system provides valuable insights for future applications in in vivo models and clinical studies.

Angiopoietins as Predictor Indexes in COVID-19 Patients in Delta and Omicron Waves.

This study aimed to explore the correlation between Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) concentrations and the Angiopoietin-2/Angiopoietin-1 ratio (Ang-2/Ang-1) with clinical outcomes, potentially serving as disease severity and survival biomarkers. A study at AHEPA University Hospital involved 90 Coronavirus Disease 2019 (COVID-19) adult patients, 30 hospitalized intensive care units (ICU), 30 inward units (non-ICU), and 30 asymptomatic non-hospitalized individuals as controls. Estimated endothelial dysfunction markers related to angiogenesis were measured. There was a statistically significant difference only between outpatient and hospitalized patients (non-ICU-ICU groups) for the Ang-1 and Ang-2 indices. The Ang-2/Ang-1 ratio has differed significantly among the individual patient groups. An ROC analysis was conducted to find an optimal threshold for distinguishing between (outpatients-non-ICU) and (non-ICU-ICU) groups. It was based on Youden's index of 0.1122 and 0.3825, respectively. The Ang-1, Ang-2 levels, and Ang-2/Ang-1 ratio were analyzed as severity indicators in COVID-19 patients. The Ang-2/Ang-1 ratio demonstrated better prognostic and diagnostic utility than individual biomarker levels. Monitoring the Ang-2/Ang-1 ratio can identify COVID-19 patients at risk and assist clinicians in tailoring treatment strategies to improve outcomes.

The Effectiveness of Adipose Tissue-Derived Mesenchymal Stem Cells Mixed with Platelet-Rich Plasma in the Healing of Inflammatory Bowel Anastomoses: A Pre-Clinical Study in Rats.

Introduction: Multiple factors have been linked with increased risk of anastomotic leak in bowel surgery, including infections, inflammatory bowel disease, patient comorbidities and poor surgical technique. The aim of this study was to investigate the positive effect, if any, of adipose derived mesenchymal stem cells (MSCs) mixed with platelet-rich plasma (PRP) in the healing of bowel anastomoses, in an inflammatory environment after establishment of experimental colitis. Materials and Methods: Thirty-five male Wistar rats were divided into five groups of seven animals: normal controls, colitis controls, PRP, MSCs, and PRP+MSCs. All groups underwent laparotomy, one-cm segmental colectomy and anastomosis in situ. In the colitis group, colectomy was performed at the affected area. Colitis was previously established by transrectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) except for the normal controls. Post-mortem histopathological, tissue hydroxyproline and anastomotic bursting pressure (ABP) assessments were performed. The Mann-Whitney U test was used to assess statistical significance differences between groups. Results: No perioperative mortality was noted. Tissue hydroxyproline and ABP were significantly increased in the group of PRP+MSCs compared to colitis controls (p = 0.0151 and p = 0.0104, respectively). Inflammatory cell infiltration was lower and fibroblast activity higher in PRP+MSCs group, but not statistically significant (p > 0.05). Neoangiogenesis (p = 0.0073) and anastomotic area epithelialization (p = 0.0182) were significantly higher in PRP + MSCs group compared to colitis controls. Discussion: The synergistic effect of the PRP and MSCs is apparently responsible for the improved healing markers in bowel anastomoses even on inflammatory bowel. This gives hope for primary anastomoses and stoma saving in many emergency and/or elective circumstances, especially in immunocompromised or malnourished patients, even in cases with inflammation or peritonitis. Clinical studies should follow in order to support the clinical application of PRP+MSCs in gastrointestinal anastomoses.

Sexual function scores are associated with arterial stiffness in postmenopausal women.

BACKGROUND: Female sexual dysfunction (FSD) has been suggested to be correlated with the burden of cardiovascular risk factors. AIM: We aimed to evaluate the possible association between functional indices of vascular function and FSD scores in apparently healthy postmenopausal women. METHODS: This cross-sectional study included 116 postmenopausal women who underwent assessment of endothelial function with measurement of flow-mediated dilation (FMD) of the branchial artery and arterial stiffness estimation with measurement of the carotid-femoral pulse wave velocity (PWV). We used the Greene Climacteric Scale to evaluate vasomotor symptomatology, the Female Sexual Function Index (FSFI) to evaluate FSD and the Beck Depression Inventory to evaluate mood disorder. Low sexual function was defined as an FSFI score <26.55. OUTCOMES: These included FSFI and low sexual function scores as well as measures of PWV and FMD. RESULTS: Sexual function scores were associated with measures of blood pressure (normal vs low sexual function; systolic blood pressure: 120.2 ± 15.0 mm Hg vs 113.4 ± 14.6 mm Hg; analysis of covariance P = .026; diastolic blood pressure: 75.9 ± 10.5 mm Hg vs 70.3 ± 9.9 mm Hg; analysis of covariance P = .012; both adjusted for age, body mass index, current smoking, and PWV). Systolic blood pressure, but not diastolic blood pressure, was associated with FSFI (B = 0.249, P = .041) and PWV (B = 0.392, P < .001). PWV measures were associated with FSFI (B = -0.291, P = .047) and pulse pressure (B = 0.355, P = .017). FMD measures were also associated with FSFI (B = 0.427, P = .033). All models were adjusted for age, body mass index, current smoking, insulin resistance, vasomotor symptomatology, and Beck Depression Inventory. CLINICAL IMPLICATIONS: Our findings demonstrate that lower scores of sexual function are associated with deteriorated vascular function mainly manifested as arterial stiffening, further contributing to systolic blood pressure changes. STRENGTHS AND LIMITATIONS: The strength of this study is the carefully selected healthy sample of postmenopausal women, with simultaneous assessment of climacteric symptomatology and mood disorders. The limitations include the small sample size, the cross-sectional design, and the recruitment of consecutive outpatients of a university menopause clinic. CONCLUSION: Longitudinal studies and interventions to improve FSD should further assess the clinical relevance of these findings.

Comparison Between EPI DWI and PROPELLER DWI in Brain MR Imaging.

OBJECTIVE: EPI DWI is a routinely used sequence in brain imaging but it has limitations when it comes to SNR and artifact reduction. PROPELLER DWI has the benefit of improving image quality compared to EPI DWI. The aim of this study is to compare the EPI DWI sequence in brain MR imaging with the PROPELLER DWI sequence. The objective is to identify which sequence is more beneficial in brain imaging by evaluating image quality and the depiction of pathologies. MATERIALS AND METHODS: A total of 101 patients (55 females and 46 males, mean age 56 years) underwent brain MRI examination on a 1.5 T scanner. EPI DWI and PROPELLER DWI sequences were acquired in every exam and were reviewed by 2 radiologists. The images were evaluated by performing a quantitative analysis based on Relative Contrast and a qualitative analysis (overall image quality, conspicuousness of lesions, artifact reduction, etc.). RESULTS: In both the qualitative and quantitative analysis PROPELLER DWI achieved better results than EPI DWI. PROPELLER DWI showed statistical significance in the overall image quality (P < 0.001), the elimination of susceptibility (P < 0.001) and flow pulsation artifacts (P < 0.001), as well as in the contrast between CSF with white (P < 0.001) and grey matter (P < 0.001). Also, PROPELLER DWI presented better delineation of pathologies like ischemic strokes, metastasis, tumors and vasogenic edemas than conventional EPI DWI. CONCLUSION: PROPELLER DWI was the preferred sequence during the image evaluation. Compared to EPI DWI, PROPELLER DWI managed to reduce susceptibility and flow pulsation whilst achieving higher image quality and lesion delineation and earlier depiction of ischemic strokes than the conventional EPI DWI. PROPELLER DWI may be incorporated in brain MR imaging replacing EPI DWI.

Radiomics Texture Analysis of Bone Marrow Alterations in MRI Knee Examinations.

Accurate diagnosis and timely intervention are key to addressing common knee conditions effectively. In this work, we aim to identify textural changes in knee lesions based on bone marrow edema (BME), injury (INJ), and osteoarthritis (OST). One hundred and twenty-one MRI knee examinations were selected. Cases were divided into three groups based on radiological findings: forty-one in the BME, thirty-seven in the INJ, and forty-three in the OST groups. From each ROI, eighty-one radiomic descriptors were calculated, encoding texture information. The results suggested differences in the texture characteristics of regions of interest (ROIs) extracted from PD-FSE and STIR sequences. We observed that the ROIs associated with BME exhibited greater local contrast and a wider range of structural diversity compared to the ROIs corresponding to OST. When it comes to STIR sequences, the ROIs related to BME showed higher uniformity in terms of both signal intensity and the variability of local structures compared to the INJ ROIs. A combined radiomic descriptor managed to achieve a high separation ability, with AUC of 0.93 ± 0.02 in the test set. Radiomics analysis may provide a non-invasive and quantitative means to assess the spatial distribution and heterogeneity of bone marrow edema, aiding in its early detection and characterization.

Overcoming phenotypic switching: targeting protein-protein interactions in cancer.

Alternative protein-protein interactions (PPIs) arising from mutations or post-translational modifications (PTMs), termed phenotypic switching (PS), are critical for the transmission of alternative pathogenic signals and are particularly significant in cancer. In recent years, PPIs have emerged as promising targets for rational drug design, primarily because their high specificity facilitates targeting of disease-related signaling pathways. However, obstacles exist at the molecular level that arise from the properties of the interaction interfaces and the propensity of small molecule drugs to interact with more than one cleft surface. The difficulty in identifying small molecules that act as activators or inhibitors to counteract the biological effects of mutations raises issues that have not been encountered before. For example, small molecules can bind tightly but may not act as drugs or bind to multiple sites (interaction promiscuity). Another reason is the absence of significant clefts on protein surfaces; if a pocket is present, it may be too small, or its geometry may prevent binding. PS, which arises from oncogenic (alternative) signaling, causes drug resistance and forms the basis for the systemic robustness of tumors. In this review, the properties of PPI interfaces relevant to the design and development of targeting drugs are examined. In addition, the interactions between three tyrosine kinase inhibitors (TKIs) employed as drugs are discussed. Finally, potential novel targets of one of these drugs were identified in silico.

A Study of DNA Methylation of Bladder Cancer Biomarkers in the Urine of Patients with Neurogenic Lower Urinary Tract Dysfunction.

Background: Bladder cancer (BCa) in patients suffering from neurogenic lower urinary tract dysfunction (NLUTD) is a significant concern due to its advanced stage at diagnosis and high mortality rate. Currently, there is a scarcity of specific guidelines for BCa screening in these patients. The development of urine biomarkers for BCa seems to be an attractive non-invasive method of screening or risk stratification in this patient population. DNA methylation is an epigenetic modification, resulting in the transcriptional silencing of tumor suppression genes, that is frequently detected in the urine of BCa patients. Objectives: We aimed to investigate DNA hypermethylation in five gene promoters, previously associated with BCa, in the urine of NLUTD patients, and in comparison with healthy controls. Design, setting and participants: This was a prospective case-control study that recruited neurourology outpatients from a public teaching hospital who had suffered from NLUTD for at least 5 years. They all underwent cystoscopy combined with biopsy for BCa screening following written informed consent. DNA was extracted and DNA methylation was assessed for the RASSF1, RARß, DAPK, TERT and APC gene promoters via quantitative methylation-specific PCR in urine specimens from the patients and controls. Results: Forty-one patients of mixed NLUTD etiology and 35 controls were enrolled. DNA was detected in 36 patients' urine specimens and in those of 22 controls. In the urine specimens, DNA was hypermethylated in at least one of five gene promoters in 17/36 patients and in 3/22 controls (47.22% vs. 13.64%, respectively, p = 0.009). RASSF1 was hypermethylated in 10/17 (58.82%) specimens with detected methylation, APC in 7/17 (41.18%), DAPK in 4/17 (23.53%), RAR-ß2 in 3/17 (17.56%) and TERT in none. According to a multivariate logistic regression analysis, NLUTD and male gender were significantly associated with hypermethylation (OR = 7.43, p = 0.007 and OR = 4.21; p = 0.04, respectively). In the tissue specimens, histology revealed TaLG BCa in two patients and urothelial squamous metaplasia in five patients. Chronic bladder inflammation was present in 35/41 bladder biopsies. Conclusions: DNA hypermethylation in a panel of five BCa-associated genes in the urine was significantly more frequent in NLUTD patients than in the controls. Our results warrant further evaluation in longitudinal studies assessing the clinical implications and possible associations between DNA hypermethylation, chronic inflammation and BCa in the NLUTD population.

Systematic characterization of therapeutic vulnerabilities in Multiple Myeloma with Amp1q reveals increased sensitivity to the combination of MCL1 and PI3K inhibitors.

The development of targeted therapy for patients with Multiple Myeloma (MM) is hampered by the low frequency of actionable genetic abnormalities. Gain or amplification of chr1q (Amp1q) is the most frequent arm-level copy number gain in patients with MM, and it is associated with higher risk of progression and death despite recent advances in therapeutics. Thus, developing targeted therapy for patients with MM and Amp1q stands to benefit a large portion of patients in need of more effective management. Here, we employed large-scale dependency screens and drug screens to systematically characterize the therapeutic vulnerabilities of MM with Amp1q and showed increased sensitivity to the combination of MCL1 and PI3K inhibitors. Using single-cell RNA sequencing, we compared subclones with and without Amp1q within the same patient tumors and showed that Amp1q is associated with higher levels of MCL1 and the PI3K pathway. Furthermore, by isolating isogenic clones with different copy number for part of the chr1q arm, we showed increased sensitivity to MCL1 and PI3K inhibitors with arm-level gain. Lastly, we demonstrated synergy between MCL1 and PI3K inhibitors and dissected their mechanism of action in MM with Amp1q.

Diet Quality and Nutritional Risk Based on the FIGO Nutrition Checklist among Greek Pregnant Women: A Cross-Sectional Routine Antenatal Care Study.

The International Federation of Gynecology and Obstetrics (FIGO) nutrition checklist is a tool for everyday antenatal clinical practice, easy to use by most healthcare professionals, aiming to initiate a conversation regarding gestational weight gain (GWG) and nutrition and identify women who might require further assessment. The present cross-sectional study aimed to apply the FIGO nutrition checklist to pregnant women attending routine antenatal care and identify nutritional risk factors. Pregnant women (n = 200) were recruited from the outpatient pregnancy clinics of two hospitals in Thessaloniki and completed the checklist. The FIGO-diet quality score and the FIGO-nutritional risk score (NRS) were calculated. The results revealed that 99% of the women exhibited at least one nutritional risk factor based on the checklist. The median FIGO diet quality score of the sample was 4.0 (3.0-5.0), with 95% of the participants responding negatively to at least one question, indicating the need for improving diet quality. Improved diet quality was noted in cases of hyperemesis gravidarum and among those receiving vitamin D supplements. A large percentage of the participants (36%) exhibited five or more nutritional risk factors, as indicated by a total FIGO-NRS below 5. Women with low middle-upper arm circumference, indicative of protein-energy malnutrition (20.6% of the sample), exhibited more nutritional risk factors compared with the rest. On the other hand, being in the third trimester of pregnancy was associated with lower nutritional risk and, subsequently, better diet quality.

MYeHealthAppCY: A Healthcare Mobile Application in Cyprus.

This paper presents MYeHealthAppCY, an mHealth solution designed to provide patients and healthcare providers in Cyprus with access to medical data. The application includes features such as an at-a-glance view of patient summary, comprehensive prescription management, teleconsultation, and the ability to store and access European Digital COVID Certificates (EUDCC). The application is an integral part of the eHealth4U platform targeting to implement a prototype EHR platform for national use. The application developed is based on FHIR and follows a strict adherence to widely used coding standards. The application was evaluated receiving satisfactory scores; however, significant work is still needed to deploy the application in production.

eHealth4U: A DEMO of a Prototype National Electronic Health Record for Cyprus.

In this paper we present a demonstration of a prototype national Electronic Health Record platform for Cyprus. This prototype is developed using the HL7 FHIR interoperability standard in combination with terminologies widely adopted by the clinical community such as the SNOMED CT and the LOINC. The system is organized in such a way to be user-friendly for its users, being the doctors and the citizens. The health-related data of this EHR are separated into three main sections, being the "Medical History", the "Clinical Examination" and the "Laboratory results". Business requirements include the Patient Summary as defined by the guidelines of the eHealth network and the International Patient Summary which are used as the base for all the sections of our EHR, together with additional medical information and functionality such as the organization of medical teams or the history of medical visits and episodes of care. From the doctor's point of view, one can search for patients who have granted the doctor with a consent and read or add/edit their EHR data by initiating a new visit as defined in the Cyprus National Law for eHealth. At the same time, doctors can organize their medical teams by managing the locations of each team and the members that belong to each team.

MAF functions as a pioneer transcription factor that initiates and sustains myelomagenesis.

Deregulated expression of lineage-affiliated transcription factors (TFs) is a major mechanism of oncogenesis. However, how the deregulation of nonlineage affiliated TF affects chromatin to initiate oncogenic transcriptional programs is not well-known. To address this, we studied the chromatin effects imposed by oncogenic MAF as the cancer-initiating driver in the plasma cell cancer multiple myeloma. We found that the ectopically expressed MAF endows myeloma plasma cells with migratory and proliferative transcriptional potential. This potential is regulated by the activation of enhancers and superenhancers, previously inactive in healthy B cells and plasma cells, and the cooperation of MAF with the plasma cell-defining TF IRF4. Forced ectopic MAF expression confirms the de novo ability of oncogenic MAF to convert transcriptionally inert chromatin to active chromatin with the features of superenhancers, leading to the activation of the MAF-specific oncogenic transcriptome and the acquisition of cancer-related cellular phenotypes such as CCR1-dependent cell migration. These findings establish oncogenic MAF as a pioneer transcription factor that can initiate as well as sustain oncogenic transcriptomes and cancer phenotypes. However, despite its pioneer function, myeloma cells remain MAF-dependent, thus validating oncogenic MAF as a therapeutic target that would be able to circumvent the challenges of subsequent genetic diversification driving disease relapse and drug resistance.

PCSK9 Inhibition in Atherosclerotic Cardiovascular Disease.

Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) represent a novel class of hypolipidemic drugs, providing an additional therapeutic option over conventional hypolipidemic treatments. Given the constantly lowering recommended LDL-C goals, low goal achievement rate and low compliance with treatment, new hypolipidemic drug classes may substantially contribute to residual risk reduction for atherosclerotic cardiovascular disease (ASCVD). This review aims to summarize contemporary evidence on the clinical role of PCSK9i in ASCVD prevention. PubMed and MEDLINE databases were searched for keywords in studies on PCSK9i and ASCVD. Approved PCSK9i are the monoclonal antibodies (Mabs), evolocumab and alirocumab, targeting PCSK9, and inclisiran, a small interfering RNA inhibiting PSCK9 synthesis. Overall, PCSK9i effectively reduced LDL-C and other atherogenic lipoproteins, including apolipoprotein B and lipoprotein( a) primarily. PSCK9i Mabs improved imaging markers reflecting coronary atherosclerotic plaque vulnerability and reduced ASCVD events in high-risk patients after short-term treatment (< 3 years follow-up). They are currently indicated as a third-line treatment for secondary prevention and primary prevention in patients with familial hypercholesterolemia at high risk of not achieving their LDL-C goals. Patients with higher baseline ASCVD risk receive greater benefits from PCSK9i. Recent evidence suggests that evolocumab was effective and safe after long-term treatment. Ongoing trials investigate new therapeutic indications for PCSK9i while their cost-effectiveness is still being considered. PCSK9i is a novel hypolipidemic drug class currently indicated for reducing residual risk in secondary ASCVD prevention and high-risk patients.

A Survey on Quantitative Risk Estimation Approaches for Secure and Usable User Authentication on Smartphones.

Mobile user authentication acts as the first line of defense, establishing confidence in the claimed identity of a mobile user, which it typically does as a precondition to allowing access to resources in a mobile device. NIST states that password schemes and/or biometrics comprise the most conventional user authentication mechanisms for mobile devices. Nevertheless, recent studies point out that nowadays password-based user authentication is imposing several limitations in terms of security and usability; thus, it is no longer considered secure and convenient for the mobile users. These limitations stress the need for the development and implementation of more secure and usable user authentication methods. Alternatively, biometric-based user authentication has gained attention as a promising solution for enhancing mobile security without sacrificing usability. This category encompasses methods that utilize human physical traits (physiological biometrics) or unconscious behaviors (behavioral biometrics). In particular, risk-based continuous user authentication, relying on behavioral biometrics, appears to have the potential to increase the reliability of authentication without sacrificing usability. In this context, we firstly present fundamentals on risk-based continuous user authentication, relying on behavioral biometrics on mobile devices. Additionally, we present an extensive overview of existing quantitative risk estimation approaches (QREA) found in the literature. We do so not only for risk-based user authentication on mobile devices, but also for other security applications such as user authentication in web/cloud services, intrusion detection systems, etc., that could be possibly adopted in risk-based continuous user authentication solutions for smartphones. The target of this study is to provide a foundation for organizing research efforts toward the design and development of proper quantitative risk estimation approaches for the development of risk-based continuous user authentication solutions for smartphones. The reviewed quantitative risk estimation approaches have been divided into the following five main categories: (i) probabilistic approaches, (ii) machine learning-based approaches, (iii) fuzzy logic models, (iv) non-graph-based models, and (v) Monte Carlo simulation models. Our main findings are summarized in the table in the end of the manuscript.