Background: Autism spectrum disorder (ASD) is a persistent neurodevelopment disorder frequently co-occurring with Attention-Deficit/Hyperactivity Disorder (ADHD) and behavior-related disorders. While behavioral therapy is the first-line option to manage ASD core symptoms, pharmacological therapy is sometimes needed to treat acute problems, such as agitation and aggressive behaviors. Recent guidelines recommend neuroleptics to reduce psychomotor agitation in people with ASD. However, since children with ASD are often drug-resistant, alternative treatments are often justified. Reports from literature showed that intra-venous valproate (IV-VPA) can be effective in reducing agitation in psychiatric patients, with lower frequency of adverse events compared to convention-al treatments. However, since findings are occasionally inconsistent, IV-VPA is not an approved option in clinical psychiatry. We aim at improving the knowledge on the IV-VPA treatment option in emergency psychiatry in the pediatric age. Methods: We report the case of a 11-year-old boy suffering from a complex neurodevelopmental condition, who experienced a psychotic episode with severe aggressive and disruptive behaviors, successfully treated with IV-VPA. Besides, we conducted an up-dated literature review on this topic. Conclusion: In our case, first-line therapies proved to be ineffective. On the contrary, IV-VPA led to a safe and prompt clinical success, in line with other reports. Based on our literature review, IV-VPA can be highly effective and can reduce the risk of adverse events that frequently occur with the use of high-dose standard medications in emergency psychiatry.

CD44 is a type I transmembrane glycoprotein, which is associated with poor prognosis in various solid tumors. Since CD44 plays critical roles in tumor development by regulating cell adhesion, survival, proliferation, and stemness, it has been considered a target for tumor therapy. Anti-CD44 monoclonal antibodies (mAbs) have been developed and applied to antibody-drug conjugates and chimeric antigen receptor-T cell therapy. We previously developed anti‐pan-CD44 mAbs, C₄₄Mab-5 and C₄₄Mab-46, which can recognize both CD44 standard (CD44s) and variant isoforms. In the present study, a defucosylated mouse IgG_2a version of the anti-pan-CD44 mAbs (5-mG_2a-f and C₄₄Mab-46-mG_2a-f) was generated to evaluate the antitumor activities against CD44-positive cells. Both 5-mG_2a-f and C₄₄Mab-46-mG_2a-f recognized CD44s-overexpressed CHO-K1 (CHO/CD44s) cells and esophageal tumor cell line (KYSE770) in flow cytometry. Furthermore, both 5-mG_2a-f and C₄₄Mab-46-mG_2a-f could activate effector cells in the presence of CHO/CD44s cells and exhibited the complement‐dependent cytotoxicity against both CHO/CD44s and KYSE770 cells. Furthermore, the administration of 5-mG_2a-f and C₄₄Mab-46-mG_2a-f significantly suppressed CHO/CD44s and KYSE770 xenograft tumor development compared with the control defucosylated mouse IgG_2a. These results indicate that 5-mG_2a-f and C₄₄Mab-46-mG_2a-f could exert antitumor activities against CD44-positive cancers and could be a promising therapeutic regimen for tumors.

Novel therapies for treatment of familial dilated cardiomyopathy (DCM) are lacking. Triggers for the progression of the disorder commonly occur due to specific gene variants that affect the production of sarcomeric/cytoskeletal proteins. Generally these variants cause a decrease in tension by the myofilaments, resulting in signaling abnormalities within the micro-environment which over time result in structural and functional maladaptations leading to heart failure (HF). Current concepts support the hypothesis that the mutant sarcomere proteins induce a causal depression in the tension time integral (TTI) of linear preparations of cardiac muscle. However, molecular mechanisms underlying tension generation particularly in relation to mutant proteins and their impact on sarcomere molecular signaling, are currently the subject of controversy. Thus, there is a need for clarification as to how mutant proteins affect sarcomere molecular signaling in the etiology and progression of DCM. A main topic in this controversy is the control of the number of tension generating myosin heads reacting with the thin filament. One line of investigation proposes that this number is determined by changes in the ratio of myosin heads in a sequestered super-relaxed state (SRX) or in a disordered relaxed state (DRX) poised for force generation upon Ca-activation of the thin filament. Contrasting evidence from nanometer–micrometer-scale x-ray diffraction in intact trabeculae indicates that the SRX/DRX states may have a lesser role. Instead, the proposal is that myosin heads are in a basal OFF state in relaxation then transfer to an ON state through a mechano-sensing mechanism induced during early thin filament activation and increasing thick filament strain. Recent evidence about the modulation of these mechanisms by protein phosphorylation has also introduced a need for reconsidering control of tension. We discuss these mechanisms that lead to different ideas related to how tension is controlled and disturbed by mutant sarcomere proteins linked to DCM including cardiac myosin, myosin-binding protein C, titin filaments, and thin filaments. Resolving the various mechanisms and incorporating them into a unified concept is crucial for gaining a comprehensive understanding of DCM. This deeper understanding is not only important for diagnosis and treatment strategies with small molecules, but also for understanding the reciprocal signaling processes that occur between cardiac myocytes and their micro-environment. By unraveling these complexities, we can pave the way for improved therapeutic interventions for managing DCM.

Analysis of liquid biopsy samples can reveal a wealth of molecular as well as cellular entities circulating in various body fluids. These entities include circulating tumor cells, circulating cell-free and tumor DNA, RNA, and proteins. Detection and characterization of this genetic and proteomic material can provide crucial information on tumor characteristics, including its heterogeneity, biology, tumor progression, staging, associated gene mutations and the course of therapy. The increased use of liquid biopsy in clinical oncology offers in non-invasive manner easier tumor sampling and continuous monitoring of the disease evolution through repetitive sampling from cancer patients. The continuous monitoring offered by this method is highly relevant to the assessment of a given therapeutic regime and early detection of markers associated with possible drug resistance, which may develop in the course of the therapy. The use of proteomic approaches, including mass spectrometry-based proteomics for the analysis of biofluids extends for over three decades, yet only in the last few years such methods have found their way to clinical oncology. The non-invasive nature of liquid biopsy and the simple procedures for sample collection made this approach far more attractive than the traditional and well-established tissue biopsy. Such preference becomes more practical in the analysis of solid tumors, particularly in pediatric population. In this review we discuss some works on the emerging role of liquid biopsy analyses in clinical oncology, and how such use allows a better understanding of diagnosis, prognosis, disease evolution and response to therapy of various forms of cancer. We also discuss the role of MS-based methods in the characterization of post-translational modifications of proteins circulating in liquid biopsies.

Objective Rhinosinusitis is a chronic condition characterized by frequent episodes of recurrence; its main treatment is pharmacological and this therapy should be continued for a long time until stabilization of the problem. Some patients, however, often must resort to targeted therapies for disease recurrences, which is why targeted preventive treatments are sought. Methods In the study performed, Pistacia lentiscus oil was used. Two groups of patients were studied with endoscopy, SNOT 22 and Nasal Cytology to evaluate nasal cellularity and ciliar motility. Results Pistacia lentiscus oil has the ability to reduce mucosal inflammation, by destroying and preventing the formation of biofilm. Conclusion The study showed that daily administration of Pistacia lentiscus oil significantly reduced the presence of biofilm. Moreover, continuous use of a lentiscus oil wash significantly reduced patients’ symptoms and improved their quality of life according to the Snot 22 questionnaire.

Understanding clinical significance of variants of unknown significance (VUS) reported in next-generation sequencing (NGS) has become essential in cancer treatment. Our study examined six widely used in silico tools: PolyPhen-2, Align-GVGD, MutationTaster2, CADD, REVEL, and Chat-GPT. We utilized a dataset of gene variants known to potentially affect immune therapy. No single tool could comprehensively determine mutation variant pathogenicity. MutationTaster2021 showed the highest overall accuracy and MCC among the tools. Notably, REVEL and Chat-GPT exhibited 100% specificity, suggesting their proficiency in accurately identifying pathogenic variants and minimizing false positives. In contrast, CADD displayed optimal sensitivity, making it suitable for effectively ruling out benign variants.

Introduction Blunt carotid injuries (BCI) in pediatric trauma are quite rare. Due to the low number of cases, only a few reports and studies have been conducted on this topic. This review will discuss how frequent BCI/ BCVI on pediatric patients after blunt trauma is, what routine diagnostics look like, if a CT/ CTA scan on pediatric patients after blunt trauma is always necessary and if there are any negative health effects? Methods This literature review includes reviews, systematic reviews, case reports and original studies in english language between 1999 and 2020 that have dealt with pediatric blunt trauma and the diagnostics of BCI and BCVI. Furthermore, publications on the risk of radiation exposure on children were included in the study. For literature research, Medline (PubMed) and the Cochrane library were used. Results Pediatric BCI/ BCVI, shows an overall incidence between 0.03 – 0.5% of confirmed BCI/ BCVI cases due to pediatric blunt trauma. 1.1 – 3.5% of pediatric blunt trauma patients underwent CTA to detect BCI. Only 0.17 – 1.2% of all CTA scans shows a positive diagnosis for BCI. In children, the median volume CT dose index on a non-contrast head CT is 33 milligray, a computed tomography angiography needs at least 138 mGy. A cumulative doses of about 50 mGy almost triples the risk of leukemia, and doses of about 60 mGy triples the risk of brain cancer. Discussion Knowing that a BCI could have extensive neurologic consequences for children, it is necessary to evaluate routine pediatric diagnostics after blunt trauma. Computed tomography scans (CT) and computed tomography angiography (CTA) are mostly used in routine BCI diagnostics. However, since radiation exposure in children should be as low as reasonably achievable, it should be asked if other diagnostic methods could be used to identify risk groups. Trauma guidelines and clinical scores like the McGovern score are reflect established BCI screening options, as well as using duplex ultrasound.

Psoriasis is a chronic recurrent inflammatory autoimmune pathology, with a major genetic component and several interferences of immunological cells and their cytokines. The complex orchestration of psoriasis pathogenesis is related to the synergic effect of immune cells, polygenic alterations, the presence of autoantigens and several external factors. The major act of IL-23/IL-17 axis, strongly influencing the inflammatory pattern established during the disease activity, is visible as a continuous perpetuation of the pro-inflammatory response and keratinocyte activation and proliferation leading to the development of psoriatic lesions. Genome wide association studies (GWAS) along offered a better view of psoriasis pathogenic pathways, with approximately one third of psoriasis genetic impact on psoriasis development is associated to MHC region, with genetic loci located on chromosome 6. The most eloquent genetic factor of psoriasis, PSORS1, was identified in the MHC I site. Between the several factors involved in its complex etiology, dysbiosis, due to genetic or external stimulus, exhibiting less variety and the involvement of pathogenic bacteria, cand induce a burst of proinflammatory consequences, both cutaneous and gut microbiome being involved in psoriasis pathogenic process. A complex understanding of the major pathways that interplay in order to initiate and perpetuate psoriatic diseases and its associated comorbidities can help the current clinical practice by properly evaluating completely and individualized each patient and establish the proper therapeutic management.

Few studies have examined the dietary protein intake and sources in combination with the longitudinal changes in brain structure markers. Our study aimed to examine the association between dietary protein intake and different sources of dietary protein with the longitudinal rate of change in brain structural markers. A total of 2723 and 2679 participants from the UK Biobank were included in the analysis. The relative and absolute amounts of dietary protein intake were calculated through a 24-hour dietary recall questionnaire. The longitudinal change rates of brain structural biomarkers were computed using two waves of brain imaging data. We utilized multiple linear regression to examine the association between dietary protein and different sources and the longitudinal changes in brain structural biomarkers. Restrictive cubic splines were used to explore nonlinear relationships, and stratified and sensitivity analyses were conducted. Increasing the proportion of animal protein in dietary protein intake is associated with a slower reduction in the total hippocampus volume (THV, β: -0.02524, P<0.05), left hippocampus volume (LHV, β: -0.02435, P<0.01) and right hippocampus volume (RHV, β: -0.02544, P<0.05).Higher intake of animal protein relative to plant protein is linked to a lower atrophy rate in THV (β: -0.01249, P<0.05) and LHV (β: -0.01173, P<0.05) and RHV (β: -0.01193, P<0.05). Individuals with higher intake of seafood exhibit lower longitudinal rate of change in HV compared to those with no consume (THV, β: -0.004514; P<0.05; RHV, β: -0.005527, P<0.05). In subgroup and sensitivity analyses, there was not a significantly alteration. A moderate increase in the intake and proportion of animal protein in the diet, especially from seafood, is associated with a lower longitudinal change rate in hippocampus volume.

Background and Objectives: In this current state, Type 2 Diabetes Mellitus (T2DM) is more prevalent in the population, and metformin is used as a first-line medication for treating it. There was up surge in the utilization of alternative therapies in the management of diabetes. Especially in diabetes, Herbal medicines are considered safe and reliable by majority of the population. Aim: The purpose of this research is aimed to estimate the safety and efficacy of Polyherbal Metabolite Compounds (PHMC) capsules in adults with T2DM. Materials and Methods: In this study, 60 T2DM patients aged 18-60 years were randomly assigned to Groups A (30) receiving Metformin 500 mg twice a day after food and Group B (30) receiving PHMC capsule 500 mg twice a day after food in a prospective, randomized and open-label clinical study. The in-silico simulation study was performed to selected plants major compounds on target protein Insulin-like Growth Factor-1 (1K3A). Result: The PHMC is found to be safe and effective in the management of T2DM. The FBS, PPBS and HbA1c were significantly lowered (p

A screening questionnaire for autism symptoms is not yet available in Poland, and there are no recommendations regarding screening for developmental disorders in Polish primary health care. The aim of the study was to assess the opinions of parents and physicians on the legitimacy and ne-cessity of screening for autism spectrum disorders, potential barriers to the implementation of the screening program, and the evaluation and presenting the process of the online ASD screen-ing, which was part of the validation program of the Polish version of one of the screening tools. The study involved 418 parents whose children were screened online and 95 primary care physi-cians who expressed their opinions in prepared surveys. The results indicate that both parents and doctors perceive the need to screen children for ASD in general population without a clear preference as to the screening method (online or in-person). Online screening may prove to be at least a partial method of solving numerous indicated systemic difficulties - including: time con-straints, lack of experienced specialists in the field of developmental disorders or related to the organizational difficulties of health care.

Pancreatic cancer stands out as one of the most lethal forms of malignancies, representing 2% of all cancer cases and contributing to 5% of cancer-related fatalities. Therefore, early detection of pancreatic cancer is crucial for enhancing treatment outcomes. Various hereditary cancer syndromes have been linked to an elevated risk of developing pancreatic cancer, suggesting potential benefits from surveillance strategies for individuals at risk. Presently, precision medicine employs PARP inhibitor therapy for pancreatic cancer patients carrying germline variants in Homologous Recombination Repair (HRR) genes. Our objective was to ascertain the occurrence of germline pathogenic/likely pathogenic variants in genes predisposing to cancer among pancreatic cancer patients. Methodologically, we analyzed 184 pancreatic cancer patients referred to our laboratory for genetic examination. Utilizing a Next-Generation Sequencing (NGS) approach, we scrutinized 52 genes implicated in hereditary cancer predisposition. Our findings revealed that 21% of the patients analyzed harbored germline pathogenic/likely pathogenic variants. Within this subset, 48% exhibited positive results in pancreatic cancer susceptibility genes, namely ATM (17%), BRCA1 (12%), BRCA2 (7%), CDKN2A (7%), and PALB2. Significantly, 64.3% of the pathogenic variants were associated with genes involved in the HRR pathway (ATM, BRCA1, BRCA2, BRIP1, CHEK2, FANCL, MRE11, PALB2, RAD50, RAD51B and RAD51C). In conclusion, our study underscores the significance of multigene genetic testing for pancreatic cancer patients, with 21% of individuals yielding findings linked to pancreatic or other cancer predisposition. Moreover, patients carried pathogenic/likely pathogenic variants in HRR genes, potentially benefiting from targeted therapies such as PARP inhibitors or platinum-based treatments.

The bioactive marine sulfated polysaccharides ulvan and carrageenan, formulated in gels at 1.5, 5.0 and 10% w/w concentrations, were evaluated for their wound healing potential on second-degree burn wounds. The polysaccharide-based gels were administered on the burn-inflamed skin of hairless female SKH-hr2 mice, and the therapeutic effect of the various treatments was assessed based on histopathological analysis, the clinical condition of mice, photo-documentation, evaluation of biophysical skin parameters, and FT-IR spectroscopy.Clinical and histopathological assessment, as well as the reduction rate of the burn wound area, indicated that the 10% w/w carrageenan gel significantly enhanced wound healing, especially at the early stages of the healing process, recovering both the α-helix of collagen and the glycosaminoglycans configuration as evidenced by the FT-IR absorption bandsof skin in vivo and ex vivo. At later stages, the healing effect of the 5% w/w ulvan gel was also notably significant, indicating that carrageenan and ulvan wound dressing gels could potentially contribute to the efficient wound healing of burn wounds.

Autoimmune kidney diseases arise from a loss of tolerance to antigens, often with unclear triggers. In this review we explore the role of the gut microbiome and how disease, diet and therapy can alter the gut microbiota consortium. Perturbations in the gut microbiota may induce the translocation of microbiota-derived inflammatory molecules such as liposaccharide (LPS) and other toxins systemically by penetrating the gut epithelial barrier. Once in the blood stream these pro-inflammatory mediators activate immune cells which release pro-inflammatory molecules many of which are antigens in autoimmune diseases. The ratio of gut bacteria Bacteroidetes:Firmicutes is associated with worse outcomes in multiple autoimmune kidney diseases including Lupus nephritis, MPO-ANCA vasculitis and Goodpasture’s syndrome. Therapies which enhance short chain fatty acid (SCFA)-producing bacteria in the gut have powerful therapeutic potential. Dietary fibre is fermented by gut bacteria which in turn release SCFAs which protect the gut barrier as well as modulate immune responses towards a tolerogenic anti-inflammatory state. Herein, we describe where the current field of research is and the strategies to harness the gut microbiome as potential therapy.

Keywords: retinoblastoma, RB, gastric inhibitory polypeptide receptor, GIPR, trefoil factor family peptide, TFF1, CAM, tumorigenesis, MK0893, miR5-542-5p

Introduction: Hospitalization in a COVID-19 unit represents a significant source of stress and psychological distress for patients. Our study aims to determine the factors of psychological distress in the therapeutic and psychosocial management of patients hospitalized with a COVID-19 infection. Methods: This cross-sectional study was carried out over 8 months at the COVID-19 zone of the CHU HASSAN II of FES. 99 patients were evaluated within days of diagnosis by psychometric scales of anxiety, depression, and post-traumatic stress. In the course of this follow-up, we found the presence of psychological impacts in these patients, and we tried to find correlating factors between the occurrence of psychiatric disorders and the set of factors related to sociodemographic data, hospitalization course and treatments taken, as well as family support. Results: 35% of patients had scores in favor of post-traumatic stress disorder, 37% of the patients had definite depression and 50% had anxiety. Post-traumatic stress, depression, and anxiety were correlated with sociodemographic factors, hospitalization, treatments received, and length of stay. Conclusion: The prevalence of anxiety-depressive disorders and post-traumatic stress disorder was high in patients with COVID-19, hence the interest in providing psychological and psychosocial care in the emergency department.

Background: Chronic lateral epicondylitis challenges the therapeutical approach; underlying mechanisms are incompletely understood; neuropathic pain and central and peripheral sensitization may explain the fact that botulinum toxin was found to play a role in pain and function management. Methods: We searched the literature for MeSH terms: lateral epicondylitis or synonyms and botulinum toxin. Results: We found 14 papers containing trials on botulinum toxin injection into the tendon or into the extensor muscles (particularly extensor carpi radialis brevis and extensor communis digitorum). We followed the administration pathways, doses, timing and side effects. Conclusion: With chronic course, the focus of the therapy shifts from the afflicted tendon to the inserting muscles, as muscle contracture may create a vicious loop to perpetuate and aggravate the disease. Doses, timing and side effects are discussed.

Lung cancer is the leading cause of cancer related mortality worldwide. In order to improve its overall survival, early diagnosis is required. Since current screening methods still face some pitfalls, such as high false positive rates for low-dose computed tomography, researchers are still looking for early biomarkers to complement existing screening techniques in order to provide a safe, faster and more accurate diagnosis. Biomarkers are biological molecules found in body fluids, such as plasma, that can be used to diagnose a condition or disease. Metabolomics has already shown to be a powerful tool in the search for cancer biomarkers since cancer cells are characterised by impaired metabolism, resulting in an adapted plasma metabolite profile. The metabolite profile can be determined using nuclear magnetic resonance, or NMR. Although metabolomics and NMR metabolite profiling of blood plasma are still under investigation, there is already evidence for its potential for early-stage lung cancer diagnosis, therapy response, and follow-up monitoring. This review highlights some key breakthroughs in this research field, where the most significant biomarkers will be discussed in relation with their metabolic pathways and in light of the altered cancer metabolism.

Procedural Sedation and Analgesia (PSA) in the Emergency Department (ED) presents a crucial aspect of emergency medicine, enabling the execution of painful or distressing procedures with minimal patient discomfort. This narrative review delineates the pharmacological framework, methodologies, and clinical considerations integral to optimizing PSA, with a particular focus on pediatric and geriatric populations. Through a comprehensive review and analysis of current practices, this work evaluates the pharmacokinetics and pharmacodynamics of widely utilized sedatives and analgesics, including propofol, ketamine, dexmedetomidine, fentanyl, midazolam, etomidate, nitrous oxide, and remimazolam. Special attention is dedicated to the selection criteria based on patient-specific risk factors, procedural requirements, and the management of potential adverse effects. The manuscript also explores innovative sedation techniques and the integration of new pharmacological agents, emphasizing evidence-based approaches to enhance patient safety and outcome. Results underscore the significance of tailored sedation strategies, especially for vulnerable groups such as pediatric and geriatric patients, highlighting the need for meticulous pre-procedural assessment and monitoring to mitigate risks. Conclusions drawn advocate for a nuanced application of PSA, guided by current evidence and clinical guidelines, to improve the quality of care in emergency settings. This research reinforces the imperative for ongoing education, skill development, and adaptation of new evidence into clinical practice to advance procedural sedation and analgesia in the ED.

Several epidemiological studies and intervention trials have demonstrated that flavanols present in grapes and blueberries can lower the risk of cardiovascular disease. However, the mechanisms of action of these compounds remain unclear due to their low bioavailability. A polyphenol-rich grape and blueberry extract (PEGB) contained about 16% flavanol, of which 11% was monomer and 4% was dimer. A sensory test investigated the oral perception of a PEGB. At concentrations where quercetin had almost no detectable taste, PEGB exhibited significant astringency. Furthermore, in comparing the redox properties against O2･- using a luminescence method, PEGB acted as a prooxidant at low concentrations, promoting O2･-production and scavenging O2･-at high concentrations under pH conditions similar to oral cavity and intestine. In contrast, quercetin showed antioxidant activity at any concentration. A single oral administration of PEGB to rats showed a significant increase in skeletal muscle arteriolar blood flow. According to these results, PEGB containing flavanols displays a potent astringent flavor, increases O2･-production at low concentrations in a neutral pH environment as well as oral and intestine, and considerably enhances blood flow to skeletal muscles after a single dose in rats. The results of this study indicate a need to investigate the causal relationship between oral perception, redox properties, and bioactivity of polyphenols.

This investigation aimed to explore the impact of acute and regular physical exercise on Brain-Derived Neurotrophic Factor (BDNF) levels in individuals with obesity. Using the Population, Intervention, Comparator, Outcome, and Study design (PICOS) approach, the inclusion criteria were defined as follows: i) population - individuals with overweight or obesity of any age or gender; ii) intervention - acute or chronic interventions involving aerobic or anaerobic methodologies; iii) comparator - for acute effect studies, pre- and post-evaluations served as comparators, while interventions included at least one experimental group or the inclusion of a control group; iv) outcome - BDNF variability concerning the applied methodology; v) study design - restricted to experimental studies exclusively. Conducted in August 2022, the searches were carried out on PubMed, Academic Search Complete, and Web of Science. The risk of bias was assessed using the Risk of Bias in Non-randomized Studies (RoBANS) tool. Out of 98 potentially relevant articles, 16 met the eligibility criteria, encompassing 23 trials. Substantial heterogeneity was observed for both acute (I2 = 80.4%) and long-term effects (I2 = 88.7%). Additionally, RoBANS analysis indicated a low risk of bias for the included studies. The study's findings revealed a significant increase in the concentration of circulating BDNF in individuals with obesity compared to the control group following acute exercise. However, such an effect was not evident in the context of long-term physical exercise, with a small effect size (ES = 0.49) recorded in the latter scenario. The observed significant increase in BDNF levels post-acute exercise suggests a potential acute response mechanism contributing to the intricate interplay between exercise and neurotrophic factors in this population. Nevertheless, the absence of a similar effect in the context of long-term physical exercise implies a potential adaptation or ceiling effect. These findings underscore the importance of considering both the duration and nature of exercise interventions when exploring the neurobiological responses associated with obesity and exercise. The study provides valuable insights for future research and clinical implications in understanding the nuanced relationship between exercise, neurotrophic factors, and obesity.

Duct-dependent lesions are classically divided into duct dependent pulmonary circulation which involves severe right sided obstructive lesions such as pulmonary atresia or critical stenosis, and duct dependent systemic circulation which is characterized by malformation of the left side of the heart, and whose severest spectrum is hypoplastic left heart syndrome. Dextro-transposition of the great arteries remains in gray zone between being included in some old classifications as a duct dependent pulmonary circulation lesion or a new category of duct-dependent or independent mixing lesion. We hypothesize that re-classifying duct dependent congenital defects into duct dependent perfusion and oxygenation offers a model to fit D-TGA into the same category of right sided obstructive lesions and reflects the clinical spectrum in a more comprehensive way.

Dystonia and tremor are distinct movement disorders, but they overlap in certain circumstances. First, dystonia and tremor may co-exist in the same individual, in the same or different regions of the body. Second, dystonic movements are sometimes rapid and repetitive, and they may mimic tremor. The term dystonic tremor first appeared in the literature to describe a rapid and repetitive dystonic movement that mimicked tremor but could be discriminated from essential tremor. With the first consensus statement on tremor, the term dystonic tremor was instead used to describe any combination of dystonia with tremor in the same body region, a definition retained in the latest consensus statement. Both definitions continue to be used in the modern literature. To address this problem, a group of specialists in dystonia and tremor met to review the problem and develop recommendations for more consistent approach. The group agreed that a terminology that could be applied in the clinic was essential, even though laboratory-based measures may sometimes be required. The group also agreed that the term tremor should exclusively refer to rhythmic movements, and the establishment of boundaries for rhythmicity is needed. The group also agreed that repetitive movements that are grossly arrhythmic in the context of dystonia, should be called jerky dystonia, rather than terms that imply tremor. Moreover, when both tremor and dystonia coexist, they should be described according to affected body regions rather than given distinct labels.

Introduction: Anterior cervical discectomy and fusion (ACDF) for cervical disc herniation (CDH) is commonly performed. Specific postoperative complications include dysphagia, dysphonia, cervicalgia, adjacent segment disorder, cage subsidence, and infections. However, interscapular pain is commonly reported by these patients after surgery, although its mechanisms have been not clarified yet. Methods: This retrospective series of 31 patients undergoing ACDF for CDH at a single Academic Hospital. Baseline and postoperative clinical, radiological, and surgical data were analyzed. The linear regression analysis was conducted to identify any factor independently influencing the occurrence rate of postoperative interscapular pain. Results: The mean age was 57.6±10.8 years, and the M:F ratio was 2.1. The preoperative mean VAS-arm was 7.15±0.81 among the 20 patients reporting brachialgia, and the mean VAS-neck was 4.36±1.43 among those 9 patients reporting cervicalgia. At 1 month interscapular pain was still reported by 8 out of the 17 patients who experienced it postoperatively, and it was recovered in all patients after 2 months. The regression analysis showed how the interscapular pain was not directly associated to age(p=0,74), gender(p=0,46), smoking status(p=0,44), diabetes(0,42), preoperative brachialgia(p=0,21) or cervicalgia(p=0,48), symptoms duration(p=0,13), baseline VAS-arm(p=0,11), VAS-neck(p=0,93), or mJOA(p=0,63) scores, or disc height modification(p=0,90). However, the postoperative increase of the mean zygapophyseal joint rims distance was identified as an independent factor in determining interscapular pain (p=0,02). Conclusions: Our study revealed that the onset of interscapular pain following ACDF may be determined by over-distraction of the zygapophyseal joints rim. Then, proper sizing of prosthetic implants could reduce this painful complication.

Over the last several years, large-scale cancer genomics studies involving multi region, multi-sample sequencing indicate that most or at least many cancer patients may have one or more “clonal" mutations in their tumors. Clonal mutations are those that are present in all of a patient’s cancer cells. They can be identified via multiregion, multisample biopsies - or circulating tumor cells/cell-free DNA. Achilles Therapeutics is currently the only company targeting patient-specific, clonal mutations. They have opted to utilize an immunotherapy approach. However, I recently devised another approach for exploiting clonal mutations called “Oncolytic Vector Replication Contingent on Omnipresent Mutation Engagement” (OVERCOME). It is based on the identification of patient-specific, clonal mutations and targeting them using a bioengineered facultative intracellular bacterium. It would be initially non-replicating, but transiently regain the ability to replicate (and also transiently become hyper-virulent) upon mutation detection via molecular switches.

Fractional flow reserve (FFR) is well recognized as a gold standard measure for the estimation of functional coronary stenosis. Technological progressions in image processing have empowered the reconstruction of three-dimensional models of the coronary arteries via both non-invasive imaging modalities, such as Coronary Computed Tomography Angiography (CCTA), and invasive coronary angiography or intravascular imaging. The application of computational fluid dynamics (CFD) techniques to coronary 3D anatomical models allows the virtual evaluation of the hemodynamic significance of a coronary lesion with high diagnostic accuracy in comparison to the invasive FFR using pressure wires. These opportunities providing hemodynamic information based on anatomy have given rise to a new era of functional angiography and coronary imaging. However, further validations are needed to overcome several scientific and computational challenges before these methods are applied in everyday clinical practice. This review aims to present all the data on the studies and methodologies that have been presented for the virtual estimation of FFR, and the diagnostic execution of the virtual tools for the hemodynamic assessment of coronary lesions compared to the invasive FFR.

Tinea incognito is a kind of skin infection that is caused by a fungus which has been changed by the use of topical or systemic steroids or other immunosuppressive medications. This alteration in the typical clinical presentation of the infection makes it difficult to diagnose for general practitioners and dermatologists. Delayed diagnosis, spread of the infection to critical body surfaces, resistance to antifungal drugs, and increased costs due to prolonged hospitalization and multiple treatment regimens often complicate tinea incognito. This condition can affect individuals of all ages and genders, but it is more common in children. Tinea incognito is a type of fungal skin infection that can present with various and non-specific clinical features, such as sudden onset of itching in an area that was previously unaffected, making it challenging to differentiate from other diseases such as eczema, seborrheic dermatitis, lupus erythematosus, psoriasis, or other non-fungal skin conditions. The treatment of tinea incognito usually involves stopping the use of topical steroids or other immunosuppressive medications. Preventive measures and management of the underlying fungal infection are necessary and can be achieved with antifungal drugs. Patients should wear loose cotton clothes, use boiling water for laundry, and iron their clothing before wearing them. Additionally, they should avoid sharing bed linens, towels, clothes, and shoes. This review aims to raise awareness of tinea incognito among health practitioners, provide tips for suspecting the disorder, include it in the differentials, and evaluate the available diagnostic procedures. The therapy utilized in published studies is also reviewed.

Introduction: The emergency of the SARS-CoV-2 virus spread and its subsequent global pan-demic have raised significant concerns regarding its impact on pregnancy outcomes. This review aims to summarize the emerging data on the risk of preterm delivery in pregnant women infected with SARS-CoV-2. Materials and Methods: A systematic search was conducted from March 2020 to December 2023 using PubMed, following PRISMA guidelines. Studies correlating maternal COVID-19 infection with preterm birth were included. Results: Thirteen studies were analyzed, indicating a higher incidence of preterm birth in SARS-CoV-2 positive pregnant women compared to controls. The average incidence rate of pre-term birth in infected patients was 18.5%, with a median of 12.75%, while non infected women showed an average incidence of preterm birth of 10% with a median of 8.2%. Discussion: Studies suggest an association between SARS-CoV-2 infection during pregnancy and increased risk of preterm birth and cesarean section. Severity of symptoms and underlying comorbidities further elevate this risk. Notably, infections during the third trimester pose the highest risk of preterm birth. Conclusion: Preventing SARS-CoV-2 infection during pregnancy is crucial to mitigate adverse obstetric outcomes. Close monitoring and tailored interventions for infected pregnant women, particularly those in later trimesters and with comorbidities, are imperative to reduce the risk of preterm birth and improve maternal-fetal outcomes.

Background: The effect of COVID-19 infection, versus the indirect effect of the pandemic on body composition remains unclear. This study investigates long-term changes in body composition in COVID–19 survivors compared to a contemporary control group. Method: This is a prospective study involving adults who had a pre-pandemic whole-body DXA scan (DXA#1) performed between 2017 and 2019. Participants were asked to return for a repeat whole-body DXA scan (DXA#2) after the pandemic. Detailed data were collected including medical and COVID history. Inflammation markers and fasting lipids were measured. For those participants who had a COVID-19 infection between the 2 DXAs, DXA#2 was acquired at least one year after COVID-19 infection. Results: Overall, 160 adults were enrolled; 32.5% females, 51.8% non-white, with mean age of 43.2 years. Half (n=80) of the participants had documented COVID infection between their 2 DXA scans (COVID+ group), and the other half never had COVID. COVID-negative participants had an increase in annualized trunk fat (g) [922.5 vs. 159.7; P=0.01], total fat (g) [1564.3 vs. 199.9; P=0.2], and LBM (g) [974.9 vs. -64.5; P=0.0002], when compared to COVID+ group. However, among the COVID+ group, no differences were seen in annualized trunk fat, total fat mass, or LBM between those with PASC and without (p>0.05). Conclusion: During the pandemic, both COVID-19-survivors and COVID-negative groups exhibited increases in weight, and total and trunk fat, likely associated with pandemic-linked lifestyle modifications. However, only COVID-19-survivors had a decline in lean body mass over the same period, regardless of PASC symptoms.

Previous investigations have illuminated the significant association between the gut microbiome and a broad spectrum of health conditions, including obesity, diabetes, cardiovascular diseases, and psychiatric disorders. Evidence from certain studies suggests that dysbiosis of the gut microbiota may play a role in the etiology of obesity and diabetes. Moreover, it is acknowledged that dietary habits, pharmacological interventions, psychological stress, and other exogenous factors can substantially influence the gut microbial composition. For instance, a diet rich in fiber has been demonstrated to increase the population of beneficial bacteria, whereas the consumption of antibiotics can reduce these advantageous microbial communities. In light of the established correlation between the gut microbiome and various pathologies, strategically altering the gut microbial profile represents an emerging therapeutic approach. This can be accomplished through the administration of probiotics or prebiotics, which aim to refine the gut microbiota and, consequently, mitigate the manifestations of associated diseases. The present manuscript evaluates recent literature on the relationship between gut microbiota and metabolic syndrome published over the past three years and anticipates future directions in this evolving field.

Introduction: Accommodation is the ability of the eye to change its refractive power (by altering the curvature of the crystalline lens) with the aim of focusing on different distances. In modern times, close working distances require good accommodation to ensure quality work without vision problems. However, dysfunction in accommodation is not uncommon. Specifically, accommodation insufficiency is the most common dysfunction associated with accommodation that can be observed at any age. Accommodation insufficiency is characterized by the eye's inability to reach its maximum potential for accommodation (amplitude of accommodation) based on age, with many individuals experiencing deviations equal to or greater than 2 diopters (2D) from the theoretically normal range. Finally, measuring the amplitude of accommodation and near vision tests should be established in routine eye examinations, as life now involves a variety of different distances. Objective: To record the rates of accommodative insufficiency in young Caucasian adults. Methods: The method used was minus to blur, and the comparison charts were based on Donder's and Hofstetter's values. Depending on the result, they were categorized as "normal," which refers to deviations from zero to 1 diopter (1D) (due to the fact that minus lenses underestimate or are quite strict regarding the range of accommodation compared to other methods in free space (e.g., push-up); "borderline," which refers to deviations from 1.25D to 1.75D or 2D with at least one eye deviating by less than 1.75D; and "accommodation insufficiency," which refers to deviations greater than 2D from the expected values, as proposed in other studies. Results: The results show a significant percentage of accommodation insufficiency in these age groups, with the percentage exceeding 50%. Additionally, men had significantly lower rates of normal accommodation amplitude compared to women. Further research is needed to study the role of refractive errors in accommodation problems. Conclusions: In a broader context, accommodation insufficiency appears to be a significant issue in young age groups, and additional studies should be conducted to analyze the problem in depth and determine its prevalence. Furthermore, a universal system for measuring the range of accommodation should be established to obtain safer results. Additionally, it would be interesting to observe the role and contribution of the ciliary muscle in the accommodation process in young adults, as theoretically, the crystalline lens is almost transparent, the issue with adaptation primarily concerns the majority's inability of the ciliary muscle to function effectively.

The sheer number of gene variants and the extent of the observed clinical and molecular heterogeneity recorded in neuropsychiatric disorders (NPDs), could be due to the magnified downstream effects initiated by a smaller group of genomic higher order alterations in response to endogenous or environmental stress. Chromosomal common fragile sites (CFS) are functionally linked with microRNA’s, gene copy number variants (CNVs), sub-microscopic deletions and duplications of DNA, rare single-nucleotide variants (SNVs/SNPs) and small insertions/deletions (indels), as well as chromosomal translocations, gene duplications, altered methylation, microRNA and L1 transposon activity and 3-D chromosomal topology characteristics. These genomic structural features have been linked with various NPDs in mostly isolated reports, and have usually only been viewed as areas harboring potential candidate genes of interest. The suggestion to use a higher level entry point, (the ‘fragilome’ and associated features), activated by a central mechanism (‘stress’) for studying NPD genetics, has the potential to unify the existing vast number of different observations in this field. This approach may explain the continuum of gene findings distributed between affected and unaffected individuals, the clustering of NPD phenotypes and overlapping comorbidities, the extensive clinical and molecular heterogeneity and the association with certain other medical disorders.

Cardiovascular diseases are a broadly understood concept focusing on vascular and heart dys-function. Lack of physical exercise, type 2 diabetes, obesity, hypertension, dyslipidemia, throm-boembolism, kidney, and lung diseases all contribute to the development of heart and blood vessel dysfunction. Although effective and important, traditional treatment with diuretics, statins, beta–blockers, calcium inhibitors, ACE inhibitors, and anti–platelet drugs remain a second–line treatment after dietary intervention and lifestyle changes. Scientists worldwide are still looking for an herbal product that would be quite effective and free from side effects, either taken together or before the standard pharmacological intervention. Such herbal–originated medication therapy may include Morus alba L. (white mulberry), Elaeagnus rhamnoides (L.) A. Nelson (sea–buckthorn), Allium sativum L. (garlic), Convallaria majalis L. (lily of the valley), Leonurus cardiaca L. (mother-wort), and Crataegus spp. (hawthorn). Valuable herbal raw materials include leaves, fruits, seeds, and even thorns. This short review focuses on six herbs that can constitute an interesting and po-tential therapeutic option in the management of cardiovascular disorders.

Background: The present study investigated the outcomes and possible predictive factors of autologous bone marrow cells (BMCs) therapy in patients with „no-option“ critical limb ischaemia (CLI). It was focused on exploring the clinical background and prior statin and renin-angiotensin system (RAS)-acting agent’s pharmacotherapy related to the therapeutic efficacy of BMCs treatment. Methods: In the present study, we have reviewed thirty-three patients (mean age 64.9 ± 10 years; 31 males) with advanced CLI after failed or impossible revascularisation, who were treated with 40 ml of autologous BMCs by local intramuscular application. Patients with limb salvage and wound healing (n=22) were considered responders to BMCs therapy, and patients with limb salvage and complete ischemic wound healing (n=13) were defined as super-responders. Logistic regression models were used to screen and identify the prognostic factors, and a receiver operating characteristics (ROC) curve, a linear regression and a survival curve were drawn to determine the predictive accuracy, the correlation between the candidate predictors and the risk of major amputation. Results: Based on the univariate regression analysis, baseline C-reactive protein (CRP) and transcutaneous oxygen pressure (TcPO2) values were identified as prognostic factors of the responders, while CRP value, ankle-brachial index (ABI) and bone marrow-derived mononuclear cells (BM-MNCs) concentration were identified as prognostic factors of the super-responders. An area under the ROC curve of 0.768 indicated good discrimination for CRP ˃ 8.1 mg/L before transplantation as a predictive factor for negative clinical response. Linear regression analysis revealed a significant dependence between the levels of baseline CRP and the concentration of BM-MNCs in transplanted bone marrow. Patients taking atorvastatin before BMCs treatment (n=22) had significantly improved TcPO2 and reduced pain scale after BMCs transplant, compared to the non-atorvastatin group. Statin treatment was associated with reduced risk for major amputation. However, the difference was not statistically significant. Statin use was also associated with a significantly higher concentration of BM-MNCs in the transplanted bone marrow compared to patients without statin treatment. Patients treated with RAS-acting agents (n=20) had significantly reduced pain scale after BMCs transplant, compared to the NON-RAS group. Similar results, reduced pain scale and improved TcPO2, were achieved in patients treated with atorvastatin and RAS-acting agents (n=17) before BMCs treatment. Results of the Spearman correlation showed a significant positive correlation between CLI regression, responders, and previous therapy before BMCs transplant with RAS-acting agents alone or with atorvastatin. Conclusions: CRP and TcPO2 were prognostic factors of the responders, while CRP value, ABI and BM-MNCs concentration were identified as predictive factors of the super-responders. Atorvastatin treatment was associated with a significantly increased concentration of BM-MNCs in bone marrow concentrate and higher TcPO2 and lower pain scale after BMCs treatment in CLI patients. Similarly, reduced pain scales and improved TcPO2 were achieved in patients treated with atorvastatin and RAS-acting agents before BMCs treatment. Positive correlations between responder and previous treatment before BMCs transplant with RAS-acting agents alone or atorvastatin were significant.

Background: Previous neuroimaging studies have identified brain regions related to respiratory motor control and perception. However, little is known about the resting-state functional connectivity (FC) associated with respiratory impairment. We aimed to determine the FC involved in mild respiratory impairment without changing the saturation of percutaneous oxygen. Methods: We obtained resting-state functional magnetic resonance imaging data from 36 healthy volunteers during normal respiration and mild respiratory impairment induced by resistive load (effort breathing). ROI-to-ROI and seed-to-voxel analyses were performed using Statistical Parametric Mapping 12 and the CONN toolbox. Results: Compared to normal respiration, effort breathing activated FCs within and between the sensory perceptive area of respiration (the postcentral gyrus, anterior insular cortex (AInsula), and anterior cingulate cortex) and visual cortex (the visual occipital, occipital pole (OP), and occipital fusiform gyrus). Graph theoretical analysis showed strong centrality in the visual cortex. A significant positive correlation was observed between the dyspnoea score (modified Borg scale) and FC between the left AInsula and right OP. Conclusions: These results suggested that the FCs within the respiratory sensory area via the network hub may be neural mechanisms underlying effort breathing and modified Borg scale scores.

This study evaluated the effect of newly introduced calcium silicate-based temporary intracanal medicament Bio-C Temp and calcium hydroxide-based material UltraCal XS on the release of transforming growth factor β1 (TGF-β1) from root canal dentin. Twenty-two intact and fully developed human premolars from patients aged 15 – 18 were shaped and irrigated according to the current clinical recommendations. The teeth were then gently split in half, and the root canal dentin of paired samples was covered with Bio-C Temp or UltraCal XS. After 3 weeks of incubation, the specimens were conditioned with 17% EDTA and the collected solution was subjected to quantification of released TGF-β1 by performing ELISA. One-way analysis of variance (ANOVA), followed by Tukey’s test, was selected to determine the statistically significant differences between the groups at the 0.95 confidence level. The highest mean value of released TGF-β1 (1993.1 pg/ml) was detected in the control group, where root canal dentin was conditioned with 17% EDTA alone. Regarding experimental groups, Bio-C Temp released a statistically significant higher amount of TGF-β1 (282.14 pg/ml) compared to UltraCal XS (114.28 pg/ml; p = 0.0158). Bio-C Temp affected the release of growth factors from root canal dentin less than UltraCal XS and may therefore serve as an intracanal medicament for regenerative endodontic procedures.

Ozonated oil has several benefits for humans, as it contributes to numerous interventions, maintaining the quality of life and the well-being of individuals. Being a natural product, it has few or almost no side effects. Thus, the study aimed to verify the sensitivity and/or resistance of fixed o “Ozonated” and “Non-Ozonated” oils from Mauritia flexuosa (Buriti), Carapa guaianensis (Andiroba) and essential “Ozonated” oils from Menta piperita (Mint), Eugenia caryophyllus (Clove) in different concentrations, against internationally known bacteria from the American Type Culture Collection – ATCC, comparing with the “Non-Ozonated” versions of the respective oils, using the Agar diffusion technique. Thus, it is evident that the ozonation of the fixed oils of Buriti and Andiroba, as well as the essential oils of Mint and Clove, provided significant results, although they were statistically different. The Buriti and Andiroba oil were ineffective in inhibiting microorganisms. On the other hand, the essential oil of Mint and Clove obtained similar activity of inhibition of microorganisms. With regard to Ozonation, the Essential Oil of “Ozonated” Clove provided greater activity than the “Non-Ozonated” one, which inhibited only one tested microorganism, in addition to producing changes in its chemical composition, requiring individualized studies for the ozonation of each essential oil.

Abstract. Introduction: BMD study gives partial information on bone health in patients with TSH suppression therapy due to Differentiated Thyroid Cancer (DTC). TBS, a new parameter of bone microarchitecture is propose for bone quality study. This study analyze their long-term use in patients with DTC. Methods: BMD was measured by DXA and TBS with iNsigth software in 145 postmenopausal DTC patients. Vertebral Fractures (VFs) with a semi-quantitative x-ray method. Results: BMD at the end study was not different from initial. TBS decreased from 1.35±0.1 to 1.27±0.1 (p=0.002). PTH, Osteocalcin, and BAP were increased, suggesting increased bone remodeling. There was an increase in osteoporosis and osteopenia (40.6% and 16.5% to 46.6% and 18.6%); 31% had partially degraded and 15.1% degraded TBS changed to 48,9% and 24,8% at the end study. VFs in 30 patients, was not different in age, BMI, calcium and alcohol ingestion, smoking, radioiodine, or thyroid parameters vs. without VFs. Odds ratio for VFs increased with osteopenia (OR 2.63). Combination of TBS plus TBS did not improve discrimination. Conclusions: TBS was lowered while BMD did not differ. Percentage of osteoporosis and osteopenia and of partially degraded and degraded TBS was higher at the end study. Predominant discordance rate was found in partially degraded microarchitecture, in which the proportion of osteopenia was higher than normal or osteoporotic patients. AUC of TBS plus BMD did not improve discrimination. TBS, radioactive iodine, and sedentary lifestyle were the main differential data for patients with DTC and VFs.

Introduction: Identifying the complexity of palliative care needs is a key aspect of referral to specialised multidisciplinary early palliative care (EPC) teams. The PALCOM scale is an instrument consisting of five multidimensional assessment domains, developed in 2018 and validated in 2023, to identify the level of complexity in patients with advanced cancer. Objectives: The main objective of this study was to determine the degree of instability (likelihood of level change or death), health resource consumption and survival of patients according to the level of palliative complexity assigned at the baseline visit during a 6-month follow-up. Method: An observational, prospective, multicentre study was conducted using pooled data from the development and validation cohort of the PALCOM scale. The main outcome variables were: a) instability ratio (IR), defined as the probability of level change or death; b) emergency department visits; c) days of hospitalisation; d) hospital death; e) survival. All variables were analysed monthly according to the level of complexity assigned at the baseline visit. Results: A total of 607 patients with advanced cancer were enrolled. According to the PALCOM scale, 20% of patients were classified as low complexity, 50% as medium and 30% as high complexity. The overall IR was 45% in the low complexity group, 68% in the medium complexity group and 78% in the high complexity group (p

Background: The role of inhaled Nitric Oxide (iNO) in managing Acute Respiratory Distress Syndrome Covid-19 related (C-ARDS) is debatable. The study aimed to analyze the effect of iNO administration in patients with persistent severe hypoxia and Intensive Care Unit (ICU) mortality. Methods: This retrospective study included 98 consecutive critically ill patients with C-ARDS admitted to ICU from 1 October 2020 to 31 October 2021. Results: Of these patients, 28% had received iNO. Twelve (44.4%) were responders. Kaplan-Mayer plot shows mortality was higher in non-responders (86.6 vs 25.0%). Non-response to iNo was the most important predictive value (p. 0.01). The Receiver Operating Characteristic (ROC) curve for a percentage increase in PaO2 from baseline confirmed that it had a higher predictive value for in-hospital survival. A value of 19% can predict the death event with a sensitivity of 81.8% and a specificity of 81.2%. Conclusions: Therefore, we propose to use iNO as a vasoreactivity test for prognostic stratification in patients with persistent severe hypoxia.

Diagnosis and treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in women remain insufficient. Fluctuations of reproductive hormones during the premenstrual period, postpartum period and (peri)menopause are neglected, even though they impact ADHD symptoms and as-sociated mood disorders [1]. Therefore, we created a female-specific treatment group for women with ADHD and premenstrual worsening of ADHD and/or mood symptoms. We describe the group programme and underlying rationale, offering a qualitative analysis of the participants’ evaluation. The 7 two-weekly sessions foreground the menstrual cycle and address several ADHD-specific topics in relation to this cyclical pattern: emotional regulation; impulsivity; setting boundaries, and triggers. Concurrently, women track their menstrual cycle and (fluctuating) ADHD and mood symptoms with an adjusted premenstrual calendar. In total, 18 women (25-47yrs) participated in three consecutive groups. We analysed the evaluation of the last group. Participants experienced the group as a safe and welcoming space. Recognition was valued by all. The topics discussed were deemed valuable and the structure suited them well. Completing the premenstrual calendar augmented awareness and recognition of individual cyclical symptoms. Discussing ADHD throughout the lifespan increased self-understanding. Participants took their menstrual cycle more seriously, prioritising self-acceptance and self-care in the luteal phase of the cycle. Exploring a cyclical approach in a group setting seems to be a positive addition to treatment for female ADHD.

This work aimed to elucidate how O3 pollution causes loss of regulation of the immune response in both the brain and the intestine. In this work, we studied the effect of exposing rats to low doses of O3 on the association between the antioxidant response of superoxide dismutase (SOD) levels and nuclear factor kappa light chains of activated B cells (NFκB) as a marker of inflammation. Method: 72 Wistar rats were used, divided into six groups that received the following treatments: Control, 7, 15, 30, 60, and 90 days at O3, respectively. After treatment, tissues were extracted and processed using Western blotting, biochemical, and immunohistochemical techniques. The results indicated an increase in 4-hydroxynonenal (4HNE) and Cu/Zn-SOD, a decrease in Mn-SOD, and SOD activity in the substantia nigra, jejunum, and colon decrease. Furthermore, the translocation of NFκB to the nucleus increased in the different organs studied. In conclusion, repeated exposure to ozone alters the regulation of the antioxidant and inflammatory response in the substantia nigra and the intestine. This suggests that these responses are critical in the loss of regulation of the inflammatory response, and they respond to ozone pollution, which could be occurring in the progression of chronic degenerative diseases.

Introduction: The association of gene variants for interleukin 6(IL-6) (rs1800796), interleukin 10 (IL-10) (rs1800896) and tumor necrosis factorα (TNFα (rs1800629) with the occurrence of spontaneous preterm birth (PTB) was investigated to determine whether these genetic variants are a risk factor. Materials and methods: 199 blood samples from pregnant women who had given birth prematurely and 200 control blood samples were analyzed to determine single nucleotide polymor-phisms (SNPs) of genes for IL-6 (rs1800796), IL-10 (rs1800896) and TNFα (rs1800629). The control samples were samples from pregnant women with term delivery. Isolation of DNA was per-formed on mini-spin columns according to the manufacturer's protocol. The quality and purity of the isolated DNA were tested using a Qubit 3 fluorometer. Genotyping was performed with an ABI PRISM 7500 SDS using TaqMan SNP genotyping assays. The genotypes obtained were an-alyzed using the 7500 Software v2.3 package. Results: Carriers of the A/A genotype for the rs1800629 of the TNFα gene have 4.81 times greater chance of late-onset PTB compared to carriers of the G/G and A/G genotypes in the recessive inheritance model. The presence of the G/G genotype in the recessive inheritance model compared with the G/A and A/A genotypes for the rs1800896 of the IL-10 gene represents a potentially protective factor, with mothers in the term-birth group having an almost 2-fold lower odds of PTB in general and an almost 10-fold lower odds of early PTB. On the other hand, carriers of the A/G genotype of rs1800896 have a 1.54-fold higher chance of preterm birth in general and a 1.6-fold higher chance of late preterm birth in the super dominant inheritance model compared to the A/A and G/G genotypes in the group of mothers with PTB. In this study, no association was found between PTB and rs1800796 of the IL-6 gene. Conclusion: rs1800629 in mothers was associated with PTB. rs1800896 shows a potentially protective effect for the occurrence of PTB in this study. No association was found between PTB and rs1800796.

Background: Effective identification and management in the early stages of sepsis are critical for achieving positive outcomes. In this context, neutrophil activation status (NEUT-RI) emerges as a promising and easily interpretable parameter. This study aimed to assess the predictive value of NEUT-RI in diagnosing sepsis and to evaluate its prognostic significance in distinguishing 28-day mortality outcomes. Materials: The study is a secondary retrospective observational analysis. Clinical data upon ICU admission were collected. A control group of critically ill patients without sepsis criteria was included. Patients were divided into subgroups based on renal function for biomarker evaluation, with 28-day outcomes reported for septic and non-septic patients. Results: 200 patients were included in the study. A significant difference between the "septic" and "non-septic" groups was detected in the NEUT-RI plasma concentration (53.80 [49.65–59.05] vs. 48.00 [46.00–49.90], p< 0.001, respectively). NEUT-RI and PCT distinguished between not complicated sepsis and septic shock (PCT 1.71 [0.42 - 12.09] vs 32.59 [8.83 - 100.00], < 0.001 and NEUT-RI 51.50 [47.80 - 56.30] vs 56.20 [52.30 - 61.92], p=0.005). NEUT-RI, PCT and CRP values were significantly different in patients with “renal failure”. NEUT-RI and PCT at admission in ICU in septic group were higher in patients who died (58.80 [53.85-73.10] vs 53.05 [48.90-57.22], p=0.005 and 39.56 [17.39-83.72] vs 3.22 [0.59-32.32], p=0.002, respectively). Both NEUT-RI and PCT showed high negative predictive value and low positive predictive value. Conclusions: The inflammatory biomarkers assessed in this study offer valuable support in the early diagnosis of sepsis. NEUT-RI elevation appears particularly promising for early sepsis detection and severity discrimination upon admission

The “red code” (RD) represents the highest levels of emergency in the emergency department (ED). The study retrospectively analyzed RDs in the Regina Margherita Children’s Hospital ED, a regional referral center in north Italy, between 1 July 2020 and 30 June 2023. The aim was to describe RD characteristics and to identify significant correlations between presenting complaints and clinical management. The study includes 934 RDs (0.9% of overall ED admissions); 64% were assigned based on the Pediatric Assessment Triangle alteration. Most patients, 86.5%, followed the medical pathway, while 13.5% were surgical cases. Admission complaints were respiratory (46.9%), neuropsychiatric (26.7%), traumatic (11.8%), cardiologic (9.3%), metabolic (3.8%), and surgical (1.5%). Seventy-six per cent of patients received vascular access, and intraosseous access was obtained in 2.2% of them. In one-third of RDs, an urgent critical care evaluation was necessary, and 19% of cases required admission to the intensive care unit. The overall mortality rate was 3.4% (0.4% in ED setting). The study identified six distinct diagnostic pathways, each associated with specific characteristics in clinical presentation, management, therapeutic interventions, and outcomes: this underscored the significance of a systematic approach in improving outcomes in pediatric RD management.

Cardiomyopathies (CMPs) are a group of myocardial disorders that are characterized by structural and functional abnormalities of the heart muscle. These abnormalities occur in the absence of coronary artery disease (CAD), hypertension, valvular disease, and congenital heart disease. CMPs are an increasingly important topic in the field of cardiovascular diseases due to the complexity of their diagnosis and management. In 2023, the ESC guidelines on cardiomyopathies were first published, marking significant progress in the field. The growth of techniques such as cardiac magnetic resonance imaging (CMR) and genetics has been fueled by the development of multimodal imaging approaches. For the diagnosis of CMPs, a multimodal imaging approach, including CMR, is recommended. CMR has become the standard for non-invasive analysis of cardiac morphology and myocardial function. This document provides an overview of the role of CMR in CMPs, with a focus on tissue mapping. CMR enables the characterization of myocardial tissues and the assessment of cardiac functions. CMR sequences and techniques, such as late gadolinium enhancement (LGE) and parametric mapping, provide detailed information on tissue composition, fibrosis, edema, and myocardial perfusion. These techniques offer valuable insights for early diagnosis, prognostic evaluation, and therapeutic guidance of CMPs. The use of quantitative CMR markers enables personalized treatment plans, improving overall patient outcomes. This review aims to serve as a guide for the use of these new tools in clinical practice.

Colorectal cancer (CRC) with KRAS mutation is prone to develop metachronous metastasis. However, effective measures for prediction and prevention of such clinical issue are currently unavailable. In this study, we confirmed that KRAS mutation is a risk factor for CRC metachronous metastasis through meta-analysis and public database analysis. Based on the ICGC-AGRO database, we have constructed a risk scoring model for predicting metachronous metastasis in KRAS-mutant CRC using machine learning, which was validated in public datasets. Furthermore, we discovered that KRAS inhibitors can effectively suppress the migration and invasion capabilities of high risk CRC cells by wound healing assay and transwell experiment, which was validated ex vivo and in vivo using organoids and splenic liver metastatic mouse model. Finally, RNA sequencing, RT-qPCR, and western blots have proven that KRAS inhibitors can suppress the epithelial-mesenchymal transition (EMT) and transforming growth factor beta (TGF-beta) signaling pathway in CRC. Collectively, our study suggests that KRAS inhibitors may inhibit the metastatic ability of CRC by suppressing EMT and the TGF-beta pathway, suggesting their potential for the prevention of metachronous metastasis in CRC with KRAS mutation.

Malocclusions have a continuously increasing prevalence from a generation to another as a result of climate changes, soil, atmosphere and water pollution. All of these aspects have unfavorable consequences on the nutritional scheme. Thus, nutrition together with other etiopathogenic factors contribute to complex alterations in the somatic development of the entire organism and, implicitly, of the cephalic extremity. The study group included 4147 children from randomly selected schools from Vâlcea County, Romania. The aim of this study is to determine the prevalence of malocclusions in schoolchildren from Vâlcea County, Romania, according to the three main classes of malocclusions (according to Angle’s classification), age groups (from 6 to 10 years old and from 11 to 14 years old), gender (male and female) and place of origin (rural and urban). For Angle class I malocclusions we recorded the highest prevalence (48,78% from the total number of schoolchildren with malocclusions), followed by Angle class II malocclusions (45,85% from the total number of schoolchildren with malocclusions) and for Angle class III malocclusions we found the lowest prevalence (5,37% from the total number of schoolchildren with malocclusions).According to gender, we found the highest prevalence in female gender (29,90% from the total number of female subjects), while in male gender we recorded a prevalence of 27,70% from the total number of male subjects. Regarding the place of origin, there is a higher prevalence of malocclusions in the urban areas (29,16%). The study subgroup included 140 children randomly selected from the total number of subjects from the study group. They were included in a more advanced study. The aim is to find potential associations between the presence of malocclusions and various oral variables. Categorical variables were expressed as numerical values and percentages, and their association was evaluated with either the Chi-square test of association or homogeneity, or the Fisher Exact test. The acquired data were incorporated into a binomial logistic regression model to assess the likelihood of developing malocclusions in relation to the following variables: defective phonation, bruxism, frequency of teeth brushing, onychophagia, oral respiration, infantile deglutition, placing objects between the maxillaries, thumb sucking and salivary aspects. It is also aimed to compare the results obtained with similar ones from the specialized literature.

Background: The monocyte-phagocyte system (MPS), including monocytes/macrophages and dendritic cells (DCs), plays a key role in anti-viral immunity. We aimed to analyze the prognostic value of the MPS components on in-hospital mortality in a cohort of 58 patients (M/F ; mean ageSD years) with COVID-19 pneumonia and 22 age- and sex-matched healthy controls. Methods: We measured frequencies and absolute numbers of peripheral blood CD169+ monocytes, conventional CD1c+ and CD141+ (namely cDC2 and cDC1), and plasmacytoid CD303+ DCs by means of multi-parametric flow cytometry. A gene profile analysis of 770 immune-inflammatory related human genes and 20 SARS-CoV-2 genes was also performed. Results: Median frequencies and absolute counts of CD169-expressing monocytes were significantly higher in COVID-19 patients than in controls (p 0.04 and p 0.01, respectively). Conversely, percentages and absolute numbers of all DC subsets were markedly depleted in patients (p

Cervical cancer is caused by a persistent and high-grade infection, caused by the Human Papilloma Virus (HPV), which, when entering cervical cells, alters their physiology and generates serious lesions. HPV 18 - is among those most involved in carcinogenesis in this region, but there are still no drug treatments that cause cure or total remission of lesions caused by HPV. Knowing that L-Asparaginase is an amidohydrolase, which plays a significant role in the pharmaceutical industry, particularly in the treatment of specific cancers, due to its antitumor properties, some studies have demonstrated its cytotoxic effect against cervical cancer cells. However, the commercial version of this enzyme has side effects, such as hypersensitivity, allergic reactions and silent inactivation due to the formation of antibodies. To mitigate these adverse effects, several alternatives have been explored, including the use of L-asparaginase from other microbiological sources, which is the case with the use of the fungus Aspergillus niger, a high producer of L-asparaginase. The study investigated the influence of the type of fermentation, precipitant, purification, characterization and in vitro cytotoxicity of L-asparaginase. The results revealed that semisolid fermentation produced higher enzymatic activity and protein concentration of A. niger. The characterized enzyme showed excellent stability at pH 9.0, temperature of 50ºC, resistance to surfactants and metallic ions, and an increase in enzymatic activity was also noted with the organic solvent ethanol. Furthermore, it exhibited low cytotoxicity in GM and RAW cells, and significant cytotoxicity in HeLa cells. These findings indicate that L-asparaginase derived from Aspergillus niger may be a promising alternative for pharmaceutical production. Its attributes, including stability, activity and low toxicity in healthy cells, suggest that this modified enzyme could overcome challenges associated with antitumor therapy.

Hard tissue apposition along the root canal walls is a slow, normally occurring physiological aging process. In response to tooth wear, local deposition of hard tissue may also occur in the pulp at a slow pace. Sometimes, the rate of hard tissue deposition acceleration may seem to be uncontrolled after dental trauma, autotransplantation, and orthodontic therapy, leading to rapid partial or total obliteration of the root canal space. This situation is called calcific metamorphosis (CM) or pulp canal obliteration (PCO). Although the incidence of pulpal necrosis in these teeth is believed to be infrequent, conventional endodontic therapy in severely calcified canals poses extreme difficulties and a higher risk for procedural accidents. This article aims to review the available approaches for the predictable negotiation of calcified canals and to introduce the buckling resistance activation test (BRAT) technique.

The purpose of this study was to determine the maximum tolerated dose (MTD) for stereotactic body radiation therapy (SBRT) in the treatment of non-metastatic prostate cancer. This study was a phase 1 dose escalation trial conducted in Japan. Patients with histologically proven prostate cancer without lymph node or distant metastasis were enrolled. The prescribed doses were 42.5, 45, or 47.5 Gy in five fractions. Dose-limiting toxicity (DLT) was defined as grade (G) 3+ gastrointestinal or genitourinary toxicity within 180 days after SBRT completion and a 6 plus 6 design was used as the method of dose escalation. A total of 16 patients were enrolled, with 6 in the 42.5 Gy group and 10 in the 45 Gy group. No DLT was observed in the 42.5 Gy group. In the 45 Gy group, one patient experienced G3 rectal hemorrhage, and another had G4 rectal perforation, leading to the determination of 42.5 Gy as the MTD. None of the patients experienced biochemical recurrence or death during the follow-up period. We concluded that SBRT for non-metastatic prostate cancer at 42.5 Gy in 5 fractions could be safely performed, but a total dose of 45 Gy increased severe toxicity.

Pregnancy at advanced maternal age (AMA) is a condition of potential risk for the development of maternal-fetal complications with possible repercussions even in the long-term. Here, we analyzed the changes of plasma redox balance and the effects of plasma on human umbilical cord mesenchymal cells (hUMSCs) in AMA pregnant women (patients) at various timing of pregnancy. One hundred patients and twenty pregnant women younger than 40 years (controls) were recruited, and evaluated at various timings during pregnancy until after delivery. Plasma samples were used to measure the thiobarbituric acid reactive substances (TBARS), glutathione and nitric oxide (NO). In addition, plasma was used to stimulate the hUMSCs, which were tested for cell viability, reactive oxygen species (ROS) and NO release. The obtained results showed that throughout pregnancy until after delivery in patients the levels of plasma glutathione and NO were lower than those of controls, while those of TBARS were higher. Moreover, plasma of patients reduced cell viability and NO release, and increased ROS release in hUMSCs. Our results highlighted alterations in the redox balance and the presence of potentially harmful circulating factors in plasma of patients They could have clinical relevance for the prevention of complications related to AMA pregnancy.

Rectal cancer presents a significant burden globally, often requiring multimodal therapy for locally advanced cases. Long-course chemoradiotherapy (LCRT) and short-course radiotherapy (SCRT) followed by surgery have been conventional neoadjuvant approaches. Recent trials favor LCRT due to improved local control. However, tumor distant recurrence remains a concern, prompting exploration of Total Neoadjuvant Therapy (TNT) as a comprehensive treatment strat-egy. Immune checkpoint inhibitors (ICIs) show promise, particularly in mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) tumors, potentially revolutionizing neoadjuvant regimens. Non-operative management (NOM) represents a viable alternative post-neoadjuvant therapy for selected patients achieving clinical complete response (cCR). Additionally, monitoring minimal residual disease (MRD) using circulating tumor DNA (ctDNA) emerges as a non-invasive method for treatment response assessment. This review synthesizes current evidence on TNT, ICIs, NOM and ctDNA, elucidating their implications for rectal cancer management and highlighting avenues for future research and clinical application.

Protein tyrosine phosphatase receptor type E (PTPRE) is a member of the “classical” protein tyrosine phosphatase subfamily and regulates a variety of cellular processes in a tissue-specific manner by antagonizing the function of protein tyrosine kinases. PTPRE plays a tumorigenic role in different human cancer cells, but its role in retinoblastoma (RB), the most common malignant eye cancer in children, remains to be elucidated. Etoposide resistant RB cell lines and RB patients display significant higher PTPRE expression levels compared to chemosensitive counterparts and the healthy human retina, respectively. PTPRE promotor methylation analyses revealed that PTPRE expression in RB is not regulated via this mechanism. Lentiviral PTPRE knockdown (KD) induced a significant decrease in growth kinetics, cell viability, and anchorage independent growth of etoposide resistant Y79 and WERI RB cells. Caspase-dependent apoptosis rates were significantly increased and a re-sensitization for etoposide could be observed after PTPRE depletion. In vivo chicken chorioallantoic membrane (CAM) assays revealed decreased tumor formation capacity as well as reduced tumor size and weight following PTPRE KD. Expression levels of miR631 were significantly downregulated in etoposide resistant RB cells and patients. Transient miR631 overexpression resulted in significantly decreased PTPRE levels and concomitantly decreased proliferation and increased apoptosis levels in etoposide resistant RB cells, impacts mirroring PTPRE KD effects and indicating PTPRE regulation via this miR. Additionally, PTPRE KD led to altered phosphorylation of protein kinase SGK3 and - dependent on the cell line - also AKT and ERK1/2, suggesting potential PTPRE downstream signaling pathways. In summary, these results indicate an oncogenic role of PTPRE in chemoresistant retinoblastoma.

The aim of this study was to evaluate the use of a flexible synthetic polymer bone graft to provide implant stability in the absence of implant stability during implant placement in a dense cortical bone model. Sockets were prepared on polyurethane blocks according to the standard implant socket drilling protocol in the control group, both oversizing and deepening in group 2, and oversizing only in group 3. In groups 2 and 3, flexible synthetic polymer bone grafts were placed in the sockets prior to implant placement. The implants were placed at bone level in all groups. The highest torque value obtained was recorded as the insertion torque. 75 implant sites in 3 groups were included in the study. The torque values of the implants in the control group were significantly higher than those of the implants with the oversized and deepened sockets and the oversized-only sockets (p&lt;0.05; p&lt;0.01).The torque values of the implants with the oversized and deepened sockets were significantly higher than those of the implants with the oversized-only sockets (p&lt;0.01). In this study, flexible synthetic polymer bone graft was shown to be effective in achieving implant stability in the management of implants with loss of primary stability.

Background: The management of gestational diabetes mellitus (GDM) focuses on dietary interventions, physical activity, and pharmacological therapy. Strategies that enhance adherence to the diet could play a pivotal role in managing this population. Objective: To compare the effectiveness of outpatient nutritional guidance supplemented by digital media with exclusively standard outpatient nutritional guidance in pregnant women with GDM. Methods: This was a randomized, patient-blinded clinical trial conducted at the Diabetes and Pregnancy outpatient clinic from February 2021 to January 2023. Pregnant women with GDM were randomly allocated into two groups: the Control Group (CG) received exclusively outpatient nutritional guidance, and the Intervention Group (IG) received outpatient nutritional guidance along with reminders via WhatsApp. Dietary intake (calories, carbohydrates, lipids, proteins, and fibers) was evaluated using 24-hour dietary recalls (24HR). Glycemic control and the need for pharmacological treatment were also assessed. Mann-Whitney tests were applied to numerical variables, and Fisher's exact test or Chi-square tests were used for categorical variables. Results: 81 women were included, 34 allocated to the CG, and 47 to the IG. Patients were followed for a period of 4 to 8 weeks. Few differences were observed in glycemic control between the two groups over the follow-up period. There were no statistical differences in pharmacological therapy (p=0.498); 188 24HR were conducted in the CG and 290 in the IG. A statistically significant increase in lipid intake was observed in the IG over the follow-up period compared to the CG (p

Cancer is a disease that encompasses multiple and different malignant conditions and is among the leading causes of death in the world. Therefore, the search for new pharmacotherapeutic options and potential candidates that can be used as treatments or adjuvants to control this disease is urgent. Natural products, especially those obtained from plants, have played an important role as a source of specialized metabolites with recognized pharmacological properties against cancer, therefore, they are an excellent alternative to be used. The objective of this research was to evaluate the action of the monoterpene isoespintanol (ISO) against the human tumor cell lines MDA-MB-231, A549, DU145, A2780, A2780-cis and the non-tumor line MRC-5. Experiments with MTT and fluorescence with propidium iodide (PI), DAPI and green plasma revealed the cytotoxicity of ISO against these cells; furthermore, morphological and chromogenic studies revealed the action of ISO on cell morphology and the inhibitory capacity on reproductive viability to form colonies in MDA-MB-231 cells. Likewise, 3D experiments validated the damage in these cells caused by this monoterpene. These results serve as a basis for progress in studies of the mechanisms of action of these compounds and the development of derivatives or synthetic analogues with a better antitumor profile.

Background: Locally advanced rectal cancers (10-20%) can present with infiltration into adjacent viscera. R0 resections remain the key factor for better survival. Traditionally these cases have been managed with open surgery. There are some limitations of laparoscopic surgery in these case, which can potentially be overcome by robotic surgery. Objectives: To determine the feasibility and outcome results of robotic multi-visceral resection of stage T4 rectal carcinoma. Methods: Consecutive patients having locally advanced carcinoma of rectum, who undergone robotic multi-visceral resection as the primary treatment between 2015 -2018 were included, through our database which was maintained prospectively. All perioperative and intraoperative parameters were analyzed. Patient demographics, co-morbidities, preoperative imaging, endoscopic findings, operative data, histopathology results, postoperative hospital course and procedure related postoperative adverse events were noted and analyzed. Results: Twenty-one patients with the diagnosis of nonmetastatic locally advanced rectal cancers were operated with Robotic Si/X platform. The median body mass index was 28.5 kg/m2 (range 21-42). The mean blood loss during operation was 20 ml (range 5-200), and the mean duration of surgery was 280 min (range 240-430). The median hospital stay after operation was 6 days (range 4-25 days). On postoperative histopathology, R0 resection rate was 90.5% (19/21). Conclusions: The robotic multi-visceral en-bloc resection of stage T4 rectal carcinoma is technically feasible and oncologically safe. Advanced technical skills, accurate radiological staging and careful patient selection can allow the extension of minimal access surgery to this challenging group of patients.

Diabetes mellitus – type 2 (DM2) is a hypercoaguable state with enhanced platelets (PLTs) activation and increased clotting factor production. Simultaneously, the fibrinolytic cell system is inhibited due to formation of clots with high resistance to fibrinolysis. The stages of PLTs "activation" have been well-characterized microscopically, morphometrically and nanomechanically (by light microscope, transmisiion electron microscope - TEM, scanning electron microscope - SEM and atomic force microscope - AFM). Thrombocytes in "acivated" (pro-coagulant) state play central role in two main biological processes: hemostasis and repair of vascular vessels. Pro-coagulant PLTs participate in generation of thrombin and in development of fibrin fibers in the clot matrix. Enhanced PLTs reactivity in dibetic- (diabetes mellitus - DM2) patients is considered as a "pro-thrombotic" state. In the retrospective- and prospective- studies on the topic, the higher are the PLTs' hematometrical indices: PLTs (count), MPV (mean platelet volume), PDW (platelet distribution width), PCR (plateletcrit), as well as PLTs/Ly ratio. The PLТs parameters/indices are usefull biomarkers in early diagnosis and prognosis of DM2. The precise studies of PLTs' state of activation during DM2 might be useful for creation of new diabetes (DM2) treatment strategies and effective medicines. Using the amount of blood glucose, attached to hemoglobin (HbA1c values) as markers of glycemic control in diabetic patients, researchers have observed association between MPV and medications as Insulin, Metformin, sulphonyl ureas. Computational modellng of PLTs' activation in DM2 is also a controlling factor for thrombocyte distribution and margination in bood vessels, associated with micro- and macrovascular disease in DM2. PLTs-derived miRNAs are novel molecular biomarkers for diagnosis and prognosis of DM2, insulin resistance and diabetes complications. We have proposed (2010) oleic acid (OA) as a substance suppressing "PLT hyperactivation" and inhibiting “thrombocyte aggregation”. Antiplatelet agents, natural plant products including, could be effective in the prevention and the secondary treatment of micro- and macrovascular complications in the type 2 Diabetes mellitus. Our proposal on following up of a combination of hematological-, hemorheological- and hemostatic parameters (indices) as a new way in diagnosis, treatment, predicting and management of DM2 and its related vascular complications, probably could be more explored in future studies.

Background: Several studies recently confirmed the emergence of resistance to antimalarial drugs in sub-Saharan Africa. Multiple first-line treatment (MFT) is one of the measures envisaged to respond to the emergence and spread of this resistance. The aim of this study was to identify perceived advantages and disadvantages of several MFT deployment strategies and to better understand potential implementation drivers and barriers. Methods: A qualitative survey was conducted in seven sub-Saharan countries amongst key opinion-leaders, national decision-makers, and end users. A total of 200 individual interviews were conducted and findings were analyzed following a thematic inductive approach. Results: From a policy perspective, the new MFT intervention would require endorsement at the global, national, and regional levels to ensure its inclusion in guidelines. Funding of the MFT intervention could be a bottleneck due to costs associated with additional training of healthcare workers, adaptation of drug delivery mechanisms, and higher costs of drugs. Concerning the MFT deployment strategies, a slight preference for the segmentation strategy was expressed over the rotation and geographic approaches, due to the perception that a segmentation approach is already in place at country level. Conclusions: The findings highlighted the need for a collective approach to MFT deployment through the engagement of stakeholders at all levels of malaria management.

Atherosclerosis, a complex metabolic-immune disease characterized by a chronic inflammation driven by the buildup of lipid-rich plaques within arterial walls, has emerged as a pivotal factor in the intricate interplay between cancer and cardiovascular disease. This bidirectional relationship, marked by shared risk factors and pathophysiological mechanisms, underscores the need for a comprehensive understanding of how these two formidable health challenges intersect and influence each other. Cancer and its treatments can contribute to the progression of atherosclerosis while atherosclerosis with its inflammatory microenvironment can exert profound effects on cancer development and outcomes. Both cancer and cardiovascular disease involve intricate interactions between general and personal exposomes. In this review we want to summarize the state-of-the-art of translational data and try to show how oncologic studies on cardiotoxicity can broaden our knowledge of crucial pathways in cardiovascular biology with a positive impact on precision cardiology and cardioncology.

The right heart catheterisation constitutes the gold standard for pulmonary hypertension (PH) diagnosis. However, echocardiography remains a reliable, non-invasive, inexpensive, convenient, and easily reproducible modality not only for the preliminary screening of PH but also for PH prognosis. The aim of this review is to describe a cluster of echocardiographic parameters for the detection and prognosis of PH and analyse the challenges of echocardiography implementation in patients with suspected or established PH. The most important echocardiographic index is the calculation of pulmonary arterial systolic pressure (PASP) through the tricuspid regurgitation (TR). It has shown high correlation with invasive measurement of pulmonary pressure, but several drawbacks have questioned its accuracy. Besides this, the right ventricular outflow track acceleration time (RVOT-AT) has been proposed for PH diagnosis. A plethora of echocardiographic indices: right atrial area, pericardial effusion, the tricuspid annular plane systolic excursion (TAPSE), the TAPSE/PASP ratio, tricuspid annular systolic velocity (s′) and recently, can reflect the severity and prognosis of PH. Recent advances in echocardiography with 3-dimensional right ventricular (RV) ejection fraction, RV free wall strain and right atrial strain may further assist the prognostication of PH.

The objective of this study was to detail the monomer composition of resin-based dental materials sold in the market in 2023 and to evaluate the proportion of BPA derivatives in relation with their applications. A search on manufacturers’ websites was performed to reference resin-based dental materials currently on the market. Their monomer composition was determined from material safety data sheets and completed with a search on PubMed database. Among the 543 material compositions exploitable, 382 (70.3%) contained BPA derivatives. Among them, 56.2% contained BisGMA, 28% BisEMA, the most frequently reported. A total of 59 monomers of which 6 BPA-derivatives were found. 309 materials (56.9%) contained UDMA and 292 (53.8%) TEGDMA. Less than one third of materials identified contained no BPA derivatives. These proportions vary a lot depending on their applications with materials dedicated to dental care of young populations containing the highest proportions of BPA-derivatives monomers. The long-term effects on human health of the different monomers identified including BPA-derivatives monomers is a source of concern. For children and pregnant or lactating women arises the question to take a precautionary principle and avoid the use of resin-based dental materials likely to release BPA by opting for alternative materials.

C-C motif chemokine receptor-8 (CCR8) belongs to class A of G protein-coupled receptors (GPCRs). CCR8 interacts with the specific chemokine ligand CCL1/I-309 in humans, which is produced by various cells, including tumor-associated macrophages and regulatory T cells (Treg). CCR8 is highly expressed on Treg and T-helper 2 (T_H2) cells recruited to the inflammation site and is implicated in allergy, asthma, and cancer progression. The CCR8⁺Treg has been suggested to be an important regulator in the immunosuppressive tumor microenvironment (TME); therefore, it has been desired to develop sensitive monoclonal antibodies (mAbs) for CCR8. This study developed a specific mAb for human CCR8 (hCCR8), which is useful for flow cytometry by employing the Cell-Based Immunization and Screening (CBIS) method. The established anti-hCCR8 mAb, C₈Mab-21, (mouse IgM, kappa) reacted with hCCR8-overexpressed Chinese hamster ovary-K1 (CHO/hCCR8) cells, TALL-1 (acute T lymphoblastic leukemia), CCRF-HSB2 (human T-lymphoblastic leukemia), and natural killer cells, which express endogenous hCCR8 by flow cytometry. Furthermore, C₈Mab-21 demonstrated a moderate binding affinity for CHO/hCCR8 and TALL-1 with a dissociation constant of 6.5×10^-8 M and 2.0×10^-8 M, respectively. C₈Mab-21, which was established by the CBIS method, could be a useful tool for analyzing the hCCR8-related biological response using flow cytometry.

Background: Dermatophytosis, commonly known as tinea, poses a significant public health concern worldwide, especially in environments with poor hygiene and overcrowding, such as prisons. Despite its prevalence and impact on quality of life, there is a lack of research on the knowledge and hygiene practices regarding dermatophytosis among prisoners, particularly in Nepal. Objective: The study aimed to assess prisoners' knowledge, hygiene practice and infection status regarding dermatophytosis in Central Prison, Nepal. Methods: A descriptive cross-sectional study with a sample size of 184 respondents was designed to collect data using a validated pre-tested questionnaire from September 2023 to January 2024. The collected data was then analysed using IBM SPSS version 21. Knowledge and hygiene practices were measured on an eight and 11-point scale and rated as poor (≤4) and sound (>4), bad (≤6), and good (>6), respectively. Summary data were presented by descriptive, while Chi-square and logistic regression were used for inferential statistics at P < 0.05. Results: The findings revealed moderate knowledge among prisoners regarding dermatophytosis, with significant gaps in understanding its spread and prevention. While most prisoners recognised the importance of treatment, there were misconceptions about the inevitability of contracting dermatophytosis and the role of personal hygiene. Conclusions: Despite good knowledge levels, adherence to recommended hygiene practices was suboptimal, highlighting the need for targeted interventions. The study underscores the importance of addressing knowledge gaps, changing attitudes, and promoting hygienic practices to mitigate the burden of dermatophytosis among prisoners.

Background: Several kinds of research say that adjuvant blood glucose and blood pressure are usual, but an efficient solution for medical application count remains. This review analyzes the pandemic blood pressure and blood glucose to identify the publications which tell about the clinical practices and research gaps in systematic research.Methods: A study guides to identify the research of Blood Pressure (BP) and Blood Glucose. In order to analyze the recent innovations and research on BP and Blood glucose, the relevant publications and literature from journals were identified.Results: Co-morbidity of BP and Blood glucose is reported as very high. The commonness of blood pressure is thrice as high in type I diabetes patients and almost two times higher in type II diabetes patients when compared to others without Diabetes. The pervasiveness of getting depression is more in the female when compared with men. A detailed study about the linkage of BP and blood glucose tells that the relationship between them is not exactly clear.Limitations: Nearly all reviews providing the linkage of BP and blood glucose are with some limitations and they are not providing any clear conclusion.Conclusions: Present research tells that people having high blood glucose will have a greater chance of getting high blood pressure. More research is needed to state the linkage between BP, blood glucose, and the growth of diabetes mellitus issues and to provide support for managing Diabetes.

Groove pancreatitis represents a chronic focal form of pancreatitis affecting the zone between the pancreatic head and the duodenal „C” loop, known as the groove area. This is a rare condition that affects the pancreatic periampullary part, including the duodenum and the common bile duct, associated usually with long-term alcohol and tobacco misuse and being more frequent in men than in women. The most common clinical symptoms of groove pancreatitis include weight loss, acute abdominal pain, nausea, and jaundice. This report is about a 66 year old woman with a history of heavy smoking, presenting with weight loss, nausea, and upper abdominal pain. Contrast enhanced computed tomography revealed the existence of a chronic pancreatitis as well as the dilatation of the main pancreatic duct, a cyst of the pancreatic head and enlargement of the biliary tract. Conservatory treatment was initiated but with no improvement of symptoms. Since there was no indication for endoscopic retrograde cholangiopancreatography, we decided to perform a pancreatoduodenectomy, as surgery appears to be the single effective treatment.

A positive fluid balance may evolve to fluid overload and associate with organ dysfunctions, weaning difficulties, and increased mortality in ICU patients. We explored whether individualized fluid management, assessing fluid-responsiveness via passive leg-raising maneuver (PLR) before spontaneous breathing trial (SBT) associated with less extubation failure in ventilated patients with high fluid balance, admitted to the ICU after liver transplantation (LT). We recruited 15 LT patients in 2023. Postoperative fluid balance was +4476 [3697,5722] mL. PLRs were conducted at ICU admission (T1) and pre-SBT (T2). Cardiac index (CI) changes were recorded before and after SBT (T3). Seven patients were fluid responsive at T1, and 12 at T2. No significant differences occurred in hemodynamic, respiratory, and perfusion parameters between fluid-responsive and fluid-unresponsive patients at any time. Fluid-responsive patients at T1 and T2 increased their CI during SBT from 3.1 [2.8,3.7] to 3.7 [3.4,4.1] mL/min/m2 (p= 0.045). All fluid-responsive patients at T2 were extubated after SBT and consolidated extubation. Two out of three of fluid-unresponsive patients experienced weaning difficulties. We concluded that fluid-responsive patients post-LT may start weaning earlier and achieve successful extubation despite high postoperative fluid balance. This highlights the profound impact of personalized assessment of cardiovascular state on critical surgical patients.

Alzheimer's Disease (AD) presents a significant challenge in the wake of its multifaceted nature, characterized by cognitive decline, memory impairment, and neuroinflammation. Despite extensive research, effective pharmacological interventions remain elusive, prompting exploration into non-pharmacological approaches. Microcurrent therapy (MC), utilizing imperceptible currents, has emerged as a potent clinical protocol. While previous studies have focused on its therapeutic effects, this study investigates its impact on neuronal damage and neuroinflammation in an AD mouse model, specifically addressing potential side effects. Utilizing 5xFAD transgenic mice, we examined the effects of MC therapy on neuronal integrity and inflammation. Our findings suggest that MC therapy attenuates memory impairment and reduces neurodegeneration, as evidenced by improved performance in memory tests and preservation of neuronal structure. Additionally, MC therapy significantly decreases amyloid-beta (Aβ) plaque deposition and inhibits apoptosis, indicating its potential to mitigate AD pathology. Our study discovered that MC therapy effectively reduces glial activation by inhibiting the TLR4-MyD88-NFκB pathway, consequently leading to decreased levels of inflammatory factors TNF-α, IL-1β, and IL-6, thus implicating TLR4 in neurodegenerative disease-related neuroinflammation. Furthermore, while our study did not observe significant adverse effects, further clinical trial into potential side effects and neuroinflammatory responses associated with MC therapy is warranted.

We aimed to evaluate the association between daily dietary calcium intake and the risk of cardiovascular disease (CVD) in postmenopausal women using data from the Korean National Health and Nutrition Examination Survey (KNHANES). This cross-sectional study included 12,348 women aged 45–70 years who had reached natural menopause. They were classified into three groups according to daily dietary calcium intake: &lt; 400 mg, 400–800 mg, and &gt;800 mg. The risks of CVD, stroke, angina, and myocardial infarction were assessed in each group. Further, we performed subgroup analysis according to the post-menopause duration (≤10 vs. &gt;10 postmenopausal years). We performed logistic regression analysis with adjustment for age, menopausal age, income, urban area, education, insulin use, body mass index, hypertension, diabetes mellitus, dyslipidemia, high alcohol intake, smoking, exercise, oral contraceptive use, and hormonal therapy use. Calcium intake level was not significantly associated with the risk of CVD in the total population and the ≤10 postmenopausal years subgroup. However, in the &gt;10 postmenopausal years subgroup, daily calcium intake &gt;800 mg was associated with significantly decreased risks of all CVD (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.11–0.64), stroke (OR, 0.06; 95% CI, 0.01–0.42), and myocardial infarction (OR, 0.27; 95% CI, 0.11–0.64). Our findings suggest that a dietary calcium intake of &gt;800 mg/day decreases the risk of CVD events in women who have been menopausal for &gt;10 years.

Human papillomavirus (HPV) is one the most common sexually transmitted infections (STI), spreading through direct sexual contact to oropharynx and anogenital regions. Although most infected individuals may be asymptomatic and naturally undergo viral clearance, in some individuals’ HPV infection causes carcinogenesis of the infected epithelia. HPV now accounts for over 70% of oropharyngeal carcinomas (OPC). Over 90% of these OPC are associated with HPV 16, one of the 14 high-risk subtypes. In recent years, HPV positive (HPV+) OPC has been one of the most rapidly rising cancers, by new cancer incidence rates, especially among men. They present some unique infection driven cellular and molecular features, in comparison to other head and neck carcinomas (HNC), constituting distinct preventive, therapeutic and prognostic strategies - with significant strides made in this area. However, HPV+OPC are routinely detected at a later stage, adding to the disease burden and overall survival. In this review, we provide a summary of HPV from a STI to malignant transformation, while also parsing through the immune response environment. We further collate key literature around infection sites, diagnostics and clinical management, while throwing light on the current state of epidemiology, transmission, screening and prevention strategies. Indeed, our improving understanding of the disease’s molecular biology has added some success to the prognostic outcomes of certain HPV+OPC across clinical trials examining targeted therapeutics and immunotherapy. This work is directed towards improving our current understanding of HPV and associated oncogenic landscape, to guide screening, early detection, triaging and further prevention and management strategies.

Glioblastoma (GBM) is the most aggressive brain cancer. To model GBM in research, orthotopic brain tumor models, including syngeneic models like GL261 and genetically engineered mouse models like TRP, are used. In longitudinal studies, tumor growth and treatment response are typ-ically tracked with in vivo imaging, including bioluminescence imaging (BLI), which is quick, cost-effective, and easily quantifiable. However, BLI requires luciferase-tagged cells, and recent studies indicate that the luciferase gene can elicit an immune response, leading to tumor rejection and experimental variation. We sought to optimize the engraftment of two luciferase-expressing GBM models, GL261 Red-FLuc and TRP-mCherry-FLuc, showing differences in tumor take, with GL261 Red-FLuc cells requiring immunocompromised mice for 100% engraftment. Immuno-histochemistry and MRI revealed distinct tumor characteristics: GL261 Red-FLuc tumors were well-demarcated with densely packed cells, high mitotic activity, and vascularization. In con-trast, TRP-mCherry-FLuc tumors were large, invasive, and necrotic, with perivascular invasion. Quantifying tumor volume using the HALO® AI analysis platform yielded results comparable to manual measurements, providing a standardized and efficient approach for reliable high-throughput analysis of luciferase-expressing tumors. Our study highlights the importance of considering tumor engraftment when using luciferase-expressing GBM models, providing in-sights for preclinical research design.

Objectives: Recently, desert dust in Europe has been recognized as a cardiovascular health problem. In Spain, desert dust inflows in recent years have been associated with worsening air quality. The present study examines whether desert dust events are related to the incidence of acute coronary syndrome (ACS) in patients under 55 years of age. Methods: Data from 2416 consecutive patients admitted to a tertiary hospital due to ACS were prospectively analyzed. A case-crossover time-stratified design using Poisson conditional regression models was applied to estimate the impact of desert dust events involving particulate matter concentrations of aerodynamic diameter < 10 μm (PM10) on the incidence of ACS. Results: Desert dust intrusion on days 0 to 5 after ACS onset showed no significant association with the incidence of ACS in patients under 55 years of age. The incidence rate ratios of PM10 concentrations 1, 2, 3, 3, 4 and 5 days before ACS onset (for changes of 10 µg/m3) were 1.02 (95% CI 0.97-1.1; p = 0.41), 1.01 (95% CI 0.96-1.07; p = 0.66), 0.99 (95% CI 0.94-1.05; p = 0.78), 0.96 (95% CI 0.9-1.02; p = 0.18) and 0.97 (95% CI 0.91-1.04; p = 0.41). Conclusions: Our findings suggest that desert dust is unlikely to be related to the incidence of premature coronary heart disease.

In this case series, we examine the impact of the Titan-iR Pro® deep spectrum biotherapeutic device on brain function in healthy individuals. Here we present 15 participants, aged 26-68 years, who enrolled in this open-label study, designed to assess the effect of a single 15-minute course of deep spectrum biotherapy on brain function. Although symptom-free upon enrollment, participants had diverse medical histories with some displaying early signs of cognitive decline. As part of the evaluation, all participants engaged in electroencephalogram (EEG) recording sessions that focused on assessing event-related potential (ERP) evaluations, including audio P300 amplitudes and latencies (speeds), neurocognitive testing, and physical reaction times. Following the Titan-iR Pro intervention an improvement in EEG-based cognitive markers was observed. These results underscore the importance of further investigation into the potential of advanced and deep spectrum photobiomodulation in the prevention and treatment of cognitive decline and other neurological disorders.

Pregnancy is a complex biological process which is associated with significant metabolic and hemodynamic changes of the maternal body which allow a normal fetal growth. The inability to adapt to these changes can affect the cardiovascular health. During pregnancy, women may experience mood swings, anxiety and emotional ambivalence. These symptoms can lead to stress and have a negative impact on the mental well-being of expectant mothers. It is crucial to know the aspects that can influence the development of cardiovascular problems among pregnant women in order to manage these cases properly. The current narrative review explores and summarizes the evidence regarding the impact of stress and anxiety on cardiovascular health in pregnant women. Understanding the physiological adaptations that the body undergoes throughout pregnancy is crucial for educating and supporting individuals as well as healthcare professionals. This enables them to recognize any risk factors or pathological conditions that may exacerbate pregnant women's health. In order to reduce maternal morbidity and mortality from cardiovascular disease, a psychological and cardiovascular risk factor screening that is done either before or during pregnancy may be able to identify situations that call for particular medical and/or psychological therapies.

To elucidate the cellular immune response to coronavirus disease (COVID-19) among children, we assessed cellular immunity in 8 children post-vaccination for COVID-19 and 11 children after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, using the T-SPOT®.COVID assay for both the spike (S) and nucleocapsid (N) proteins. In the vaccinated group, the T-SPOT®.COVID assay for the S protein yielded positive results in all eight children. In contrast, in the post-infection group, the assay for the N protein was positive in 5 of 11 children, with 3 of these 5 children requiring hospital admission, including 2 who needed mechanical ventilation. Therefore, the T-SPOT®.COVID assay is valuable for assessing cellular immunity against COVID-19, and most children infected with COVID-19 may not develop such immunity unless the disease severity is significant.

Recently intraductal carcinoma of the prostate (IDCP) has attracted increasing interest owing to its unfavorable prognoses. To effectively identify the IDCP-specific gene expression profile, we took a novel approach of characterizing a typical IDCP case using spatial gene expression analysis. A formalin-fixed, paraffin-embedded sample was subjected to Visium CytAssist Spatial Gene Expression analysis. IDCP within invasive prostate cancer sites was recognized as a distinct cluster separate from other invasive cancer clusters. Highly expressed genes defining the IDCP cluster, such as MUC6, MYO16, NPY, and KLK12, reflected the aggressive nature of high-grade prostate cancer. IDCP sites also showed increased hypoxia markers HIF1A, BNIP3L, PDK1, and POGLUT1; decreased fibroblast markers COL1A2, DCN, and LUM; and decreased immune cell markers CCR5 and FCGR3A. Overall, these findings indicate that the hypoxic tumor microenvironment and reduced accessibility to immune cells, which reflect the pathological characteristics of IDCP, may influence the aggressiveness of high-grade prostate cancer.

Merkel cell carcinoma (MCC) is a rare, highly aggressive skin cancer characterized by two etiologies: the first one, observed in most cases, is attributed to Merkel cell polyomavirus (MCPyV), a DNA tumor virus, while the second one is due to ultraviolet (UV) radiation exposure. Currently, there are limited diagnostic, prognostic, and therapeutic biomarkers available for MCC. MicroRNAs (miRNAs) are small RNA molecules that do not code for proteins but regulate various cellular processes, including cell cycle progression, proliferation, differentiation, and apoptosis. The dysregulation of miRNAs has been associated with a wide range of cancers since they can act as either tumor suppressors or oncogenes. This paper aims to collect, summarize and re-organize the recent discoveries concerning miRNAs, whose dysregulation in the pathogenesis and progression of MCC is slowly emerging. Furthermore, the potential clinical applications of miRNAs as diagnostic biomarkers, possible differentiation between MCPyV-related and unrelated MCC, predictors of response to therapy and prognostics are also discussed. From this review, it emerges that miRNAs may have, in the near future, the potential to become clinically significant in improving the diagnostic accuracy, prognostic evaluation, and therapeutic options of MCCs. Finally, the new perspectives on the poorly explored field of artificial intelligence in MCC are provided.

Introduction: Atrial fibrillation (AF) is a common cardiac arrhythmia whose prevalence rises with age and is linked to increased morbidity and mortality due to the risk of thromboembolism. Management typically involves anticoagulation and rhythm control, but the treatment of elderly patients with multiple comorbidities requires careful consideration of drug side effects and interactions. Cibenzoline, a Vaughan-Williams class IA antiarrhythmic, is effective against AF but has risks of toxicity, especially in older people and those with renal impairment, due to its renal excretion and prolonged half-life in these populations. Discussion: This paper presents a case of an 80-year-old woman with paroxysmal AF who suffered cardiac arrest due to cibenzoline toxicity despite receiving standard adjusted dosages. The patient's cibenzoline blood concentration was significantly higher than the therapeutic range, leading to cardiotoxicity, which was exacerbated by drug interactions with bisoprolol and edoxaban, both metabolized by the CYP3A4 enzyme. Venoarterial extracorporeal membrane oxygenation (V-A ECMO) and intra-aortic balloon pump (IABP) successfully managed the cardiac arrest. This case emphasizes the unpredictable pharmacokinetics of cibenzoline in elderly patients with renal impairment and the need for vigilant therapeutic drug monitoring to avoid adverse events. Conclusions: Cibenzoline can pose a significant risk of severe toxicity in elderly patients with renal impairment, and drug interactions may potentiate this risk. The paper underscores the importance of careful dose adjustment and monitoring of drug levels in this population. In cases of cibenzoline-induced cardiac arrest, V-A ECMO and IABP are effective treatment modalities. The case study serves as a critical reminder for clinicians to remain vigilant for drug-induced complications and to apply aggressive supportive treatments when necessary.

Introduction The monitoring of cerebral perfusion in patients with brain damage is a major clinical challenge. Monitoring cerebral oxygenation (rSO2) by NIRS was introduced at the turn of the 1980s, and many clinicians believed it was a valuable method for assessing cerebral perfusion and subsequent measures to optimize cerebral flow. The main problem of NIRS usage is the presence of the intermediate structures-skin, skull, meninges, cerebrospinal fluid-and their influence on the outcome of the test. Therefore, it seems that NIRS assessment performed on a patient during brain death attempts, can give an idea of the magnitude of the influence of these intermediate structures on the monitoring result. Case We present a retrospective analysis of cerebral oxygenation measurements of a patient undergoing a brain death diagnostic procedure. A clinical situation where the cerebral blood flow is stopped can give an idea of the specificity of the method, particularly the impact of the influence of intermediate structures on the monitoring outcome. In this case, the NIRS result is increased by the oxygenation of the patient before the apnoea test. The influence of chromophores in the tissues surrounding the CNS, reflections and scattering of the light wave spectrum have a very significant effect on the final result of cerebral saturation measurement. Discussion The majority of research observations describing changes in cerebral perfusion or its optimisation may be burdened by the problem described, i.e. the significant influence of measured oxygenation from intermediate structures. The specificity of NIRS to assess cerebral perfusion requires careful analysis. The therapeutic implications of monitoring cerebral oxygenation with NIRS are of great importance and, from the example presented and the literature provided, the method should be used with caution. It has been shown that in a patient with brain death, the result of NIRS oxygenation measurements depends on the surrounding structures of the brain.

Excess consumption of a high-fat diet has been identified as one of the contributing factors for obesity. Women are at higher risk for adult obesity than men, predisposing them to a different set of detrimental disease conditions. Furthermore, aging studies show that physiological decline also has a serious impact on changes in the endocrine properties of white adipose tissue. Howev-er, there is still relatively little known about the factors associated with obesity and aging and their compounding impact on women’s health. To investigate adipocytokine secretion profile changes, female C3H/HeJ mice were induced to obesity through long-term consumption of a high-fat diet. Weight gain measurements and Echo MRI analysis of fat composition showed in-creases were a due solely to the high fat content in the diet. Adipocytokine secretions were ana-lyzed in media conditioned from harvested visceral fat tissue that was organ cultured ex-vivo. Adipocytokine analysis across diets and age showed significant increases in Adiponectin and Leptin secretion in high-fat diets, accelerated increases in Resistin secretion with high-fat diets. Aging induced increased secretion of Lipcalin-2, Pentraxin-3 and Serpin E1, MCP-1 and ICAM-1, regardless of diet. Furthermore, comparisons of organoid cultured protein secretions and flash-frozen tissue samples differed greatly, suggesting the WAT organoid cultures may yield information more reflective of in situ conditions. Taken together, our results show that diet and aging significantly impact secretions from adipose tissue, that may contribute to women’s health issues.

Background: The management of erectile dysfunction (ED) shows several grey zones and new treatments for reduce the percentage of patients who discontinued the treatment are required. Here, we aim to evaluate the role of a natural mixture of named Icarifil (L-Citrulline, L-Carnitine, Eruca vesicaria, Panax ginseng, Tribulus terrestris, Turnera diffusa, Taurine, Vitamin E, Zinc) in the management of patients with ED. Methods: From September 2022 to March 2023, all patients attending 3 urological institutions due to ED were randomized to receive: Icarifil 1 sachet every 24 h (Group 1) or Icarifil 1 sachet + tadalafil 5 mg 1 tablet every 24 h (Group 2) or tadalafil 5 mg 1 tablet daily (Group 3), for 3 months. All patients underwent urologic visit and dedicated questionnaires (IIEF-5, SEP-2, SEP-3) at the enrollment and at the follow-up evaluation (3 months). Patient Reported Outcomes (PROs) at the follow-up evaluation were used. Primary endpoint was the difference in the questionnaires at the follow-up visit when compared with enrollment among the study groups. Results: In the per-protocol analysis, 52 patients in the Group 1, 55 in the Group 2 and 57 in Group 3 have been analyzed. At the follow-up evaluation, IIEF-5 have been improved in all the 3 Groups between enrollment and follow-up evaluation, but a statistically significant difference has been reported between Group 2 (+7.4) versus Group 1 (+4.1) or 3 (+5.1), (p&lt;0.001; p&lt;0.001). Moreover, 47 patients (94.0%) in the Group 2 showed an improvement in the SEP questionnaires, when compared with the baseline, while 29 in the Group 1 (56.9%) and 42 in the Group 3 (82.3%) with a statistically significant difference (p=0.004; p=0.003) among the Groups. The PROs analysis reported a better efficacy and patients’ satisfaction in Group 2 when compared with Group 1 or 3. Conclusions: In conclusion, Icarifil is able to improve penile erectile function in mild–moderate ED and it is able to significantly improve the clinical efficacy of tadalafil 5 mg daily use. Icarifil could be represent an interesting alternative treatment in patients experiencing adverse effects or with contraindications for chronic treatment with PDE5-is.

Human Immunodeficiency Virus (HIV) infection and its latent recurrent infection make vaccine development a significant challenge for traditional vaccines; however, the mRNA delivery of multiepitope antigens capable of creating antibodies against the surface proteins of HIV-1 and HIV-2 along with their respective Nef proteins, responsible for the latent infection can bring a most effective, as well as affordable solution to the unresolved epidemics of HIV. In this paper, we present the complete design of a multiepitope vaccine to prevent acute infections and inactivate Nef proteins that block the MHC-1 and MHC-2 pathways to hide the virus for later reinfection.

(1) Background: Tooth extraction is one of the oldest and most well-known surgical procedures in dental medicine. It is still routinely performed to date by both general practitioners, oral surgeons, and dental undergraduates. The Benex extraction system allows for the extraction of teeth in vertical direction, which avoids most trauma against the surrounding alveolar bone and soft tissues; (2) Methods: The study included 56 patients who were recruited from the department of Oral Surgery at the Faculty of Dental Medicine, Medical University – Plovdiv. Patients were divided into two groups of 28 patients – Group I (control group) and Group II (study group). For each group the success of the extraction, buccal cortical plate preservation, pain experience and early wound healing were assessed; (3) Results: There was no statistical significance between the success of the extractions in both groups. The Benex extractions preserved the buccal cortical plate in 95% of the cases, whereas the forceps extractions only in 71.8%, which shows a statistical significance. On the seventh day patients in group II reported less pain, without a significant difference. There was a significantly bigger number of completely healed extraction wounds on the 10th day; (4) Conclusions: Atraumatic extractions allow for more hard and soft tissues to be preserved in the extraction site. This is all crucial for the successful outcome and aesthetically pleasing results of a following prosthetic or implant restoration.

Background: Cancer therapy-related cardiac dysfunction (CTRCD) is a growing concern for public health, with a growing incidence due to improved survival rates for patients with hematological malignancies due to diagnostic and therapeutic advances. Identification of patients at risk CTRCD is vital to develop preventive strategies. Methods: A single-center retrospective cohort study was conducted between 1 January 2017 and 15 February 2023. Medical records of patients with lymphoma treated with first-line anthracyclines were reviewed. Demographic data, cardiovascular risk factors, biomarkers of myocardial damage and echocardiographic information were collected. Results: A total of 200 patients were included. The incidence of CTRCD was 17.4 % (35/200). Patients with CTRCD were older than those without CTRCD, with a mean age of 65.17 years vs 56.77 (p = 0.008). Dyslipidemia (DL) (31.4% vs 13.4% p = 0.017) and previous cardiovascular disease (40% vs 13.3%, p< 0.001) were more frequent in the group who developed an event. Mean baseline NT-proBNP levels in the subgroup with cardiovascular events were 388.73 kg /L ± 101.02, and 251.518 kg /L ± 26.22 in those who did not (p = 0.004). Differences in Troponin I levels were identified during and after treatment without exceeding the laboratory’s upper reference limit. Patients were followed for a median of 51.83 months (0.76-73.49). The presence of a CTCRD event had a negative impact on overall mortality from any cause (HR = 2.23 (95% CI 1.08-2.93), p = 0.031). Conclusions: Early identification of risk factors is crucial to manage patients at risk for CTRCD.

DIEP-based breast reconstruction necessitates wide undermining at the abdominal donor-site, creating large wound areas. Flap harvesting is usually conducted using electrosurgical dissection devices. This study sought to compare the clinical outcomes in patients after using the PEAK PlasmaBlade (PPB) versus monopolar electrocautery (MPE). This retrospective cohort study included 128 patients with DIEP-based breast reconstruction. Patient characteristics as well as information on the postoperative course were collected and a comparative evaluation was conducted. The MPE group exhibited significantly (p* = 0.0324) higher abdominal drainage volume (351.11 ± 185.96 ml) compared to the PPB group (279.38 ± 183.38 ml). Subgroup analysis demonstrated that PPB significantly reduced postoperative wound fluid in patients with BMI > 30 kg/m² (p* = 0.0284), without prior neoadjuvant chemotherapy (p** = 0.0041), and among non-smokers (p = 0.0046). Furthermore, postoperative pain was significantly (p**** < 0.0001) lower in the PPB cohort. This study confirms the non-inferiority of the PEAK PlasmaBlade to conventional electrocautery for abdominal flap harvesting. The PPB demonstrated advantages, notably reduced drainage volume and lower postoperative pain levels. Recognizing patient subsets that benefit more from the PPB highlights the importance of personalized device selection based on patient characteristics.

In patients with heart failure, the evaluation of left ventricular (LV) diastolic function is vital, offering crucial insights into hemodynamic impact and prognostic accuracy. Echocardiography stands as the primary imaging modality for diastolic function assessment, and using it effectively requires a profound understanding of the underlying pathology. This review covers four main topics: first, the fundamental driving forces behind each phase of normal diastolic dynamics, along with the physiological basis of two widely used echocardiographic assessment parameters, E/e' and mitral annulus early diastolic velocity (e'); second, the intricate functional relationship between the left atrium and LV in patients with varying degrees of LV diastolic dysfunction (LVDD); third, the role of stress echocardiography in diagnosing LVDD and the significance of parameter changes in this context; and fourth, the clinical utility of evaluating diastolic function from echocardiography images across diverse cardiovascular care areas.

Background: Autonomic balance measurement (ABM) is a valuable tool in clinical practice for assessing the functioning of the autonomic nervous system (ANS), which controls involuntary bodily functions. Here we summarize the current understanding of the utility of autonomic balance measurement in clinical practice. Methods: A narrative review of relevant literature was conducted, focusing on studies investigating the use of autonomic balance measures in various clinical settings. Results: ABM holds potential benefits in clinical practice, including aiding in diagnosing autonomic dysfunction, monitoring treatment efficacy, and predicting potential health complications. ABM can be crucial for diagnosing various conditions, including cardiovascular diseases (Heart failure, arrhythmias, and hypertension), neurological disorders (Parkinson's disease, Alzheimer's disease, and diabetic neuropathy), in sports medicine athletes can undergo ABM to optimize training regimens, enhance performance, assessing the impact of training stress, preventing overtraining, and promoting overall well-being and probably to assess potential health risks, in metabolic syndromes ABM can aid in the early detection of autonomic neuropathy, a diabetes-related complication, allowing for timely intervention and better management of the disease, and psychiatric disorders (Anxiety, depression, and post-traumatic stress disorder). In addition, ABM can be helpful in monitoring of treatment efficacy, by tracking changes in autonomic balance, clinicians can assess if treatments for conditions impacting the autonomic nervous system are effective. ABM can also be helpful in predicting outcomes by facilitating early recognition of future health complications in certain populations. However, limitations exist, including non-specificity, variability in measurements, and limited evidence for routine use in specific clinical settings. Conclusion: Incorporating autonomic balance measurement into routine clinical assessments provides a more comprehensive understanding of a patient's health. It complements traditional diagnostic methods, offering additional insights into the body's regulatory mechanisms. While autonomic balance measurement offers potential benefits, careful interpretation and consideration of its limitations are crucial for its effective use in clinical practice. ABM remains a valuable and versatile tool in clinical practice for a deeper understanding of the autonomic nervous system, enabling early detection, targeted interventions, and improved management of various medical conditions across different specialties.

Background: Early postoperative airway management after laryngo-tracheal surgery is crucial. Acute respiratory failure due to glottis’ oedema may occur, requiring reintubation. This can prolong ventilatory assistance, jeopardizing the anastomosis. To date, only judicious steroid administration and fluid management are available to avoid more invasive procedures. High-Flow-Oxygen-Therapy(HFOT) is a noninvasive O2 support method providing humidification, warmed air, Positive-End-Expiratory-Pressure(AIRVO2). No data exist about HFOT use to prevent early complications after laryngo-tracheal surgery. Methods: Between Sept.2020-Sept.2022, 107 consecutive patients underwent laryngo-tracheal surgery received HFOT(Group A). Data and long-term results were compared with those of 80 patients operated between Sept.2018-Aug.2020(Group B), when HFOT was not available. All patients were operated in a single center. No pre- or post-operative settings changed, except for HFOT introduction. We analyzed and compared the risk for “delayed” reintubation (unexpected reintubation within the first 24-48 hours after extubating/laryngeal mask removal) in the two groups. Results: No patients reported HFOT-related adverse events. Control group(B) presented “delayed” reintubation in 37% (p= 0.027), Intensive Care Unit admission in 67%(p=0.005) and longer hospital stay(p=0.001) compared to HFOT group(A). Minor complications rate was 3% in both group and overall mortality was 0%. Re-stenosis was described in 4.6% of HFOT group, without a statistically significant difference (p=0.7006). Conclusions: Our study is the first to investigate HFOT use in patients undergoing laryngo-tracheal surgery, potentially representing a consistent innovation in the peri-operative management of these patients. With the limit of a retrospective series, we would suggest HFOT use for preventing post-operative reintubation rate, possibly reducing ICU admission and hospital stay.

Background: Penile squamous cell carcinoma (PSCC) is classified into two prognostically distinct types: human papillomavirus (HPV)-associated and HPV-independent. Conversely, the impact of p53 status on prognosis remains controversial. We correlated HPV and p53 status with prognosis in a large series of PSCC patients. p53 was analysed according to a recently described immunohistochemical (IHC) pattern-based framework that includes two normal (scattered, mid-epithelial) and four abnormal patterns (diffuse, basal overexpression, cytoplasmic and null) and closely correlates with TP53 mutational status. Methods: A total of 122 patients with surgically treated PSCC in three hospitals in Barcelona, Spain, were included. Based on HPV in situ hybridization and p16 and p53 IHC expression, the tumors were classified into three molecular types: HPV-associated, HPV-independent/p53 normal, and HPV-independent/p53 abnormal. All patients were followed for at least 22 months (median 56.9 months), and disease-specific survival (DSS) was analysed. Results: Thirty-six tumors (29%) were HPV-associated, 35 (29%) were HPV-independent/p53 normal, and 51 (42%) were HPV-independent/p53 abnormal. Disease-related deaths were observed in 3/36 (8%), 0/35 (0%) and 14/51 (27%) of the patients, respectively (p&lt;0.001). A total of 7/14 deaths in the latter group were patients with tumors showing p53 patterns not recognized in the classical p53 IHC interpretation (basal, null, cytoplasmic). According to our multivariate analysis, HPV-independent/p53 abnormal tumors and advanced stage were associated with impaired DSS (hazard ratio=23.4, 95% confidence interval [CI]= 2.7-3095.3; p=0.001 and 16.3, 95% CI=1.8-2151.5; p=0.008, respectively). CONCLUSION: Compared with patients with HPV-associated and HPV-independent/p53-normal PSCC, patients with HPV-independent/p53 abnormal PSCC have worse clinical outcomes. p53 IHC results define two prognostic categories in HPV-independent PSCC: HPV-independent/p53-normal tumors as low-risk tumors, whereas HPV-independent/p53-abnormal tumors as aggressive neoplasms.

Recent research has implicated the gut microbiota in the development of lymphoma. Dysbiosis of the gut microbial community can disrupt the production of gut microbial metabolites, thereby impacting host physiology and potentially contributing to lymphoma. Dysbiosis-driven release of gut microbial metabolites such as lipopolysaccharides can promote chronic inflammation, potentially elevating the risk of lymphoma. In contrast, gut microbial metabolites, such as short-chain fatty acids, have shown promise in preclinical studies by promoting regulatory T-cell function, suppressing inflammation, and preventing lymphoma. Another metabolite, urolithin A, exhibited immunomodulatory and antiproliferative properties against lymphoma cell lines in vitro. While research on the role of gut microbial metabolites in lymphoma is limited, this article emphasizes the need to comprehend their significance, including therapeutic applications, molecular mechanisms of action, and interactions with standard chemotherapies. The article also suggests promising directions for future research in this emerging lymphoma and gut microbiome investigation field.

Implant-supported-screw-retained prostheses are really popular. Some of the most frequent complications have been mechanical complications. These include abutment screw loosening or even screw fracture. Using an intermediate abutment can offer several advantages. However, little literature has been found regarding how this affects the mechanical behavior of dental restorations. This study focuses on understanding the mechanical behavior of implant-supported restorations with a transepithelial component compared to those with a direct implant-supported restoration. It was carried out by using the Finite Element Method (FEM) and was experi-mentally validated. The results showed that in the case of transepithelial-supported restoration, the prosthetic screw mounted over the transepithelial component suffers higher stress than the one screwed directly to the implant. After applying a cyclic fatigue load, it is experimentally proven that, in the transepithelial-supported restorations, the fuse changes from being the screw that goes to the implant, to being the upper one. As a conclusion we can say that the use of an intermediate abutment in dental restoration not only provides better protection to the rest of the dental restoration but also allows easier repair in the event of a fracture. This can potentially lead to more efficient procedures and improved patient outcomes.

Objectives: To study sociodemographic and clinical variables including psychiatric comorbidities in patients with irritable bowel syndrome. Methods: A total of 150 patients were screened to select 100 patients for the study who were attending a medical gastroenterology clinic in a tertiary care centre in north India. Diagnosis of IBS was made using Rome IV criteria and severity of symptoms were assessed by the Irritable Bowel Syndrome Symptom Severity Scale (IBS-SSS). Clinical evaluation was done for screening of psychiatric comorbidities and diagnosis was made as per DSM 5. Depression, Anxiety and Stress Scale - 21 Items (DASS-21) and Somatic Symptom Scale–8 (SSS-8) were used to assess depression, anxiety, stress and somatic symptoms. Result: The mean age of cases was 35.6 years and majority were i.e., 38.0% in 18-29 years. Males were 62.0% and females were 38.0%. 61.0% of the cases were diagnosed with Moderate IBS. Evaluation on DASS-21 revealed 53.0% were in moderate category in depression, 43.0% were having moderate anxiety and 36.0% were having moderate stress. 48% cases were in high category in somatic symptom scale. Psychiatric comorbidities were present in 29.0% of cases. Depressive disorders were most common psychiatric comorbidity. Conclusion: Patients with IBS presenting to tertiary care centre in Northern India were mostly young males living in semi-urban area, belonging to hindu region, married and had a nuclear family. Patients with IBS commonly have associated psychiatric disorders; anxiety disorders and depression are most common.

Background/Objectives: Patients with rheumatoid arthritis (RA) have an increased risk of infections. The risk of presenting herpes zoster (HZ) is 1.5-2 times higher than in immunocompetent individuals and disseminated presentation is more frequent. Our aim was to analyze the prevalence and general features of HZ in RA patients. Methods: Prospective study of 392 RA patients included in the vaccination program of our hospital between 2011 and 2016, and followed-up until December 2020. Diagnosis of HZ was made according to clinical manifestations: skin rash, blisters, paresthesia and local pain in one or more dermatomes. Results: We studied 392(309women/83men), mean age 59±13years. Every patient was followed-up during a mean period of 137±110 months (range: 42months- 42years). HZ infection was observed in 30 of 392 (25women/5men) patients; age (mean±SD) 64.7±11.8years. Prevalence was 7.65% in this period and incidence rate was 13.22/1000patients/year. Three patients had facial involvement, one with optic involvement and one patient presented a disseminated HZ. Seven patients presented postherpetic neuralgia treated with gabapentinoids. The main features of RA of these 30 patients were: positive RF(n=17; 56.6%), positive anti-CCP(13; 43.3%) and erosive disease(10; 33.3%). At HZ infection they were in treatment with glucocorticoids (19; 63.3%), conventional DMARDs (15; 50%), biological DMARDs (15; 50%), tofacitinib (2; 6.6%) and upadacitinib (1; 3.3%). Conclusions: HZ is a relative frequent viral complication of RA patients. In our series, one patient presented a disseminated HZ and nearly 25% of patients had post-herpetic neuralgia. Include HZ vaccine in our vaccination program in RA patients may be beneficial.

Introduction. Intra-abdominal cystic formations represent heterogeneous pathologies with varied localization and clinical manifestation. The first challenge of a giant intra-abdominal cystic lesion is identifying the organ of origin. The clinical presentation of intra-abdominal cystic lesions varies from acute manifestations to non-specific symptoms or accidental discovery. Case presentation: A 2-year-old girl presents to the emergency unit with a fever of 38.5 Celsius, loss of appetite, and apathy. The investigations showed a gigantic intra-abdominal mass whose organ belonging could not be specified. Postoperatively, a giant mesenteric lymphangioma was evident, which was completely excised. Discussions Giant cystic formations modify the anatomical reports and become space-replacing formations, and the starting point is even more challenging to assess preoperatively. Nevertheless, the careful evaluation of the characteristics of the formation, the effect on the adjacent organs, the age of the patient, and the clinical picture can provide elements of differential diagnosis.

Tumid Lupus Erythematosus has been the subject of heated debate as to its correct nosographic classification. In particular, its definition has changed over time, depending on the different studies performed. In this review we address the initial definition of TLE, the changes that have taken place in the understanding and placement within the classification of Lupus Erythematosus (LE), and focus on clinical, histopathological, immunophenotypical and differential diagnosis aspects.

Keywords: Oral health, diabetes, periodontal disease, caries, periodontitis.

Objective: To evaluate the variables influencing the length of stay (LoS) for COVID-19 ICU patients at Tygerberg Hospital (Cape Town) and to identify the covariates that significantly influenced it and any potential risk factors associated with LoS. Methods and Results: Poisson, negative binomial (NB), Hurdle–Poisson, and Hurdle–NB regression models were used to model the LoS in this prospective cohort study. The fitted models were compared using the Akaike information criterion (AIC), Vuong’s test criteria, and Rootograms. Based on the chosen performance criteria, the NB model provided the best fit outperforming other candidate models. The baseline LoS count was 8 days. On average, antibiotics reduced LoS by 0.74-fold (95% CI 0.62-0.89) compared to not taking antibiotics. The second wave had a significant effect on the average LoS, which decreased by 0.36-fold (95% CI 0.14-0.93) compared to the first wave. Average LoS increased by 1.01-fold (95% CI 1.01-1.02) for every one-year increase in the age of the patient and by 1.02-fold (95% CI 1.01-1.03) for every 1 unit increase in neutrophils. A 1 ng/L increase in log (TropT) levels decreased the average LoS by 0.87-fold (95% CI 0.81-0.93) similarly, a unit increase in the PF ratio decreased the average LoS by 0.998-fold (95% CI 0.997-0.999) respectively. Conclusion: The study identified common clinical characteristics associated with length of stay in ICU for COVID-19 patients, including age at admission, PF ratio, neutrophils, TropT, Wave, and antibiotic use. These results can aid in identifying risk factors for increased length of stay, assist in healthcare systems planning, and aid in evaluating different models for analysing this type of data.

The study aimed to evaluate implant success and bone height variations after transcrestal sinus floor elevation (tSFE) using the osseodensification technique (OD) combined with beta-tricalcium phosphate (β-TCP), as bone graft material and simultaneous implant placement. Thirteen patients requiring the placement of one implant in the upper posterior maxilla, with a residual bone height of