The differentiation between Neuromyelitis optica spectrum disorder (NMOSD) and cervical spondylotic myelopathy (CSM) is necessary, because both diseases have similar symptoms, such as motor weakness and sensory disturbances. The challenge arises when NMOSD presents with short-segment spinal cord lesions, which can mimic the clinical presentation of CSM. This case report presents an NMOSD misdiagnosed as CSM. A 66-year-old woman presented with neck pain, left arm pain, and motor weakness. She was initially diagnosed with CSM based on MRI findings that revealed the increased signal intensity of the spinal cord at the C3 to 4 levels and underwent surgery. Three years later, she had sudden left upper extremity motor weakness and mild gait disturbance. Physical exam showed left-side weakness and altered reflexes, with longitudinally extensive transverse myelitis (LETM) findings on cervical MRI. The CSF study revealed a 2+ AQP4-Ab finding. Finally, NMO was diagnosed. Steroid pulsed therapy and immunosuppression therapy led to improved motor function and gait after 20 days. We present a case report of a NMO patient who initially exhibited clinical and radiological features CSM but was later diagnosed with NMO. This case underscores the diagnostic challenge in distinguishing NMO from CSM, especially in elderly patients who commonly experience spinal degeneration leading to cord compression and associated cord signal changes on MRI. The misinterpretation or confusion with transverse myelitis can occur as a result. This case highlights the importance of considering NMO as a potential differential diagnosis in elderly patients with spinal degeneration, emphasizing the significance of precise and timely diagnosis for guiding optimal treatment decisions.

Purpose: Prostate cancer is the most common male prevalent malignancy in Europe. Biological recurrence occurs in 20-40% of patients within 10 years following treatment. [18F]F-Choline PET/CT is the most used technique for detecting recurrent disease but is rarely positive for low PSA levels. [18F]PSMA-1007 PET/CT allows early detection of recurrence sites. Methods: We conducted a prospective multicenter study. Each patient had access to a [18F]F-Choline and [18F]PSMA PET/CT. The primary endpoint was to determine the therapeutic impact of the [18F]PSMA comparative to [18F]F-Choline PET/CT. Secondary endpoints were the diagnostic performance and the correlation between PET/CT parameters and prognostic factors of prostate disease. Results: 47 patients were included. A therapeutic modification was observed in 36% of them between what the clinicians expected after the [18F]F-Choline PET/CT and what they finally decided after the [18F]PSMA PET/CT. Diagnostic performance of [18F]F-Choline was 28% versus 70% for [18F]PSMA with a significant difference. With [18F]PSMA PET/CT, there was a significative correlation between PSA level of biological recurrence and SUVmax but not between ISUP score and SUVmax of the selected lesion. Conclusion: This study found a modification in therapeutic management following [18F]PSMA PET/CT in one third of patients. This change could result in earlier and better management with detection of lesions at a lower PSA level than is possible with [18F]F-Choline.

Benign prostatic obstruction (BPH) is a common disease with male and surgical treatment is the gold standard for symptomatic disease. Prostate Artery Embolization (PAE) is one of emerging therapies which aims to minimize the lower urinary tract symptoms (LUTS) of BPH and volume of enlarged prostate. We reported here a case of 100-year-old man with 90 cm3 prostate and severe symptoms secondary to BPH, who underwent a successful PAE through distal transradial access without any complication. The patient satisfied with this treatment and no symptoms recurrence after PAE. It demonstrated that PAE was a safe and effective treatment for BPH and was indicated in elderly/ non-surgical candidate.

Objective: To evaluate the use of CDK4/6 inhibitors as a risk factor for medication-related osteonecrosis of the jaw (MRONJ) in a cohort of patients with metastatic breast cancer treated with denosumab. Methods: multicentre, retrospective, observational study. All patients with breast cancer treated with denosumab (January 2011-December 2022) were included. The relationship between CDK4/6 inhibitors and MRONJ was analysed. Results: 243 patients were included, ninety-five (44.2%) used a CDK4/6 inhibitor. There were 21 patients with MRONJ. In patients treated with denosumab without CDK4/6 inhibitors the incidence of MRONJ and mean time to the occurrence of MRONJ was 6.6% (8/120) and 16.8 months (SD 7.8) respectively. In patients treated with denosumab and CDK4/6 inhibitor 13.7% (13/95) and 15.4 month (SD 8.7) respectively. The difference in the incidence was not significant (p=0.085). Conclusion: it suggest that the incidence of MRONJ in patients with metastatic breast cancer treated with denosumab was higher and the onset of MRONJ occurred earlier in the presence of CDK4/6 inhibitors. Although the difference was not significant, given that the use of this combination is very common in routine clinical practice, it would be advisable to carry out larger prospective studies to clarify the risk of this association.

Age-related myelination decrease is considered one of the likely mechanisms of cognitive decline. The present study is based on the longitudinal assessment of global and regional myelination of the normal adult human brain using the fast macromolecular fraction (MPF) mapping. Additional markers were age-related changes in white matter (WM) hyperintensities on FLAIR-MRI and the levels of anti-myelin autoantibodies in serum. Eleven healthy subjects (33–60 years in the first study) were scanned twice, 7 years apart. An age-related decrease in MPF was found in global WM, GM, and mixed WM-GM, as well as in 48 out of 82 examined WM and GM regions. The greatest decrease in MPF was observed for the frontal WM (2-5%), genu of the corpus callosum (CC) (4.0%) and caudate nucleus (5.9%). The age-related decrease in MPF significantly correlated with an increase in the level of antibodies against myelin basic protein (MBP) in serum (r = 0.69 and r = 0.63 for global WM and mixed WM-GM, correspondingly). The volume of FLAIR hyperintensities increased with age but did not correlate with MPF changes and the levels of anti-myelin antibodies. MPF mapping showed high sensitivity to age-related changes in brain myelination, providing the feasibility of this method in clinics.

Rabson-Mendenhall syndrome is a rare autosomal recessive disorder characterized by severe insulin resistance, resulting in early-onset diabetes mellitus. We are reporting the first case of Rabson-Mendenhall syndrome in a Paraguayan patient. The patient is a 5-year-old girl who presented with hypertrichosis, acanthosis nigricans, and nephrocalcinosis. Genetic testing by NGS revealed two pathogenic variants in exons 2 and 18 of the INSR gene; c.332G>T (p. Gly111Val) and c.3485C>T (p. Ala1162Val), in combined heterozygosis. The novel INSR c. 332G>T variant leads to the substitution of glycine to valine at position 111 in the protein, and multiple in silico software predicted it as pathogenic. The c. 3485C>T variant leads to the substitution of alanine to valine at position 1162 in the protein previously described for insulin resistance and Rabson-Mendenhall syndrome. The management of Rabson-Mendenhall syndrome is particularly challenging in children, and the use of metformin is often limited by its side effects. The patient was managed with nutritional measures due to the early age of onset. This report expands the knowledge of Rabson-Mendenhall syndrome to the Paraguayan population and adds a novel pathogenic variant to the existing literature.

Postmenopausal abnormal uterine bleeding is a common clinical problem addressed in gynecological practice and should prompt clinical investigation due to the significant prevalence of malignant and premalignant lesions of endometrium in this age group. Nevertheless, other causes should be considered since its diagnostic and therapeutic management may differ considerably. Here, we present a case of a colouterine fistula due to chronic diverticulitis presenting with postmenopausal abnormal uterine bleeding. This is extremely rare and is caused by the rupture of a diverticular abscess into the uterine wall, resulting in an inflammatory adhesion of the colon and uterus, with necrosis and subsequent fistula formation. The clinical presentation is variable and may include abdominal pain, gastrointestinal tract symptoms, vaginal discharge and abnormal uterine bleeding. The laboratory and imaging techniques may be not completely conclusive and definitive diagnosis can be made intraoperatively. There are different treatment options, being the en bloc resection and primary anastomosis the most used, allowing complete treatment. The prognosis for a colouterine fistula secondary to diverticulitis is excellent after surgery. This case highlights the importance of clinical suspicion of an unusual cause of uterine bleeding and an effective and multidisciplinary approach that allowed complete surgical treatment and patient recovery.

Background: The current standard technique for vascular grafting in cerebral revascularization surgery is through the interposition of an autologous blood vessel. Technical complications have necessitated the development of a synthetic alternative, but classical biomaterials are not suited for small caliber vascular grafting due to neointimal hyperplasia and thrombosis. Electrospinning of polymers is a promising technique for the development of small vascular grafts. The in vivo performance and efficacy of electrospun polyurethane (ePU) grafts with an internal diameter of < 1.5 mm have thus far not been evaluated. Methods: We developed a novel ePU graft with a diameter of 1.25 mm for implantation into the infrarenal aorta of rats. Results: Patency rates of grafts after a four-month-period were equal to those reported in other studies with larger ePU graft diameters, and equal or higher than in studies with other biomaterials. We observed some loss in flow velocity throughout the grafts, which suggests a decreased elasticity of the graft compared to native rat aorta. However, the grafts demonstrated good neo-endothelialization and minimal neointimal hyperplasia. Their porosity promoted cellular infiltration, as shown on tissue slide examination. Conclusion: Our results show that ePU vascular grafts with internal diameter of < 1.5 mm are promising candidates for vascular grafting in cerebral revascularization surgery.

Curcumin, a major constituent of turmeric, has beneficial effects against several diseases. In cystic fibrosis (CF), this compound potentiates the activity of a number of cystic fibrosis transmembrane conductance regulator (CFTR) mutants. Despite holding promise in the treatment of CF, the curcumin binding site in CFTR and the molecular mechanism of activation of this channel are still unknown. The results of the study, based on docking and molecular dynamics (MD) simulations, allow to propose that curcumin binds the closed ATP-free CFTR near the NBD1/ ICl1/ICl4 interface. The bound ligand, once approached by NBD2 during transient channel opening, lays at a multiple interdomain cross point. Thereafter, curcumin can bridge NBD1 and NBD2, and also ICL1/ICL4 and ICL2/ICL3 finally tightening the same interdomain interactions that normally uphold the active conformation in the wild type ATP-bound CFTR. The proposed binding site is compatible with biochemical observations made in previous CFTR-curcumin interaction studies. These findings provide the framework for the design of novel drugs that activate CFTR mutants characterized by defects in ATP binding and/or NBD dimerization, or even lacking NBD2.

Type 2 diabetes (T2D) has a complex pathophysiology which makes modeling the disease difficult. We aimed to develop a novel model for simulating T2D in vitro, including hyperglycemia, hyperlipidemia, and variably elevated insulin levels targeting muscle cells. We investigated insulin resistance (IR), cellular respiration, mitochondrial morphometry and the associated function in different T2D -mimicking conditions in rodent skeletal (C2C12) and cardiac (H9C2) myotubes. Physiological controls included 5mM glucose with 20mM mannitol as osmotic controls. To mimic hyperglycemia, cells were exposed to 25mM glucose. Further treatments included insulin, palmitate, or both. After short-term (24h) or long-term (96h) exposure, we performed radioactive glucose uptake and mitochondrial function assays. Mitochondrial size and relative frequencies were assessed by morphometric analyses using electron micrographs. C2C12 and H9C2 cells treated short- or long-term with insulin and/or palmitate and HG showed IR. C2C12 myotubes exposed to T2D -mimicking conditions showed significantly decreased ATP-linked respiration and spare respiratory capacity, and less cytoplasmic area occupied by mitochondria, implying mitochondrial dysfunction. In contrast, H9C2 myotubes showed elevated ATP-linked and maximal respiration and increased cytoplasmic area occupied by mitochondria, indicating better adaptation to stress and compensatory lipid oxidation in a T2D environment. Both cell lines displayed elevated fractions of swollen/vacuolated mitochondria after T2D -mimicking treatments.Our stable and reproducible in vitro model of T2D rapidly induced IR, changes in ATP-linked respiration, shifts in energetic phenotypes, and mitochondrial morphology, which are comparable to the muscles of patients suffering from T2D. Thus, our model should allow studying disease mechanisms, potential new targets, and screen candidate therapeutic compounds.

Preterm birth (PTB), a multi-causal syndrome, is one of the global epidemics. Maternal nutrition, but also neonatal and placental telomere length (TL), are among the factors affecting PTB risk. However, the exact relationship between these factors and the PTB outcome, remains obscure. The aim of this review, was to investigate the association between PTB, maternal nutrition and placental-infant TL. Observational studies were sought, with the keywords: maternal nutrition, placenta TL, newborn, TL, and PTB. No study was found that included all keywords simultaneously, and thus, the keywords, were searched in dyads, to reach assumptive conclusions. The findings show that maternal nutrition affects PTB risk, through its influence on maternal TL. On the other hand, maternal TL independently affects PTB risk, and at the same time PTB is a major determinant of offspring TL regulation. The strength of the associations and the extent of the influence from covariates, remains to be elucidated in future research. Furthermore, the question of whether maternal TL, is simply a biomarker of maternal nutritional status and PTB risk, or a causative factor of PTB, to date, remains to be answered.

The increasing number of caesarean section (CS) is a major challenge in modern obstetrics. This rise is not supported by better neonatal and maternal outcomes. The prevention of unnecessary primary CS is a global priority. This study focuses on effectiveness and safety of yoga practice during pregnancy and it’s connection to perinatal outcome. We conducted a single-blinded, randomized controlled clinical trial, with healthy singleton primiparas, randomized at first trimester of pregnancy. A total of 214 participants were randomized, 106 in yoga and 108 in controls. The study group performed yoga exercise while the controls received standard antenatal care. The yoga exercises were performed once a week, lasted 90 minutes, under the supervision of a certified yoga teacher. All pregnant women from study group completed 12 yoga exercises. The results showed that the yoga group had a lower rate of urgent intrapartum CS (p-0.004) and more frequent spontaneous vaginal delivery (p-0.009), while the control group had a higher rate of induced labour (p-0.032). Conclusion: Yoga practice in pregnancy is a promising intervention that has a potential to decrease intrapartum urgent CS rates and assures natural and spontaneous vaginal birth; it’s highly recommendable to healthy pregnant women.

The phenomenon of decreased serum uric acid (UA) levels in patients with Parkinson’s disease (PD) and its relationship with purine metabolic pathways remain unclear. We compared inosine, hy-poxanthine, xanthine, and UA levels in serum and cerebrospinal fluid (CSF) of PD patients with those of controls, and investigated the effect of changes in the purine metabolic system on UA levels in PD. Overall, 134 samples (serum, 45 PD patients and 30 controls; CSF, 39 PD patients and 20 controls), were analyzed using liquid chromatography-tandem mass spectrometry. A general linear model (GLM) was used to investigate relationships among purine metabolites. Compared to controls, PD patients had significantly lower UA levels in the serum and CSF, and serum and CSF UA levels were significantly correlated. Additionally, in PD, decreased serum hypoxanthine levels were observed with decreased CSF inosine and hypoxanthine levels, suggesting the involvement of the purine recycling system. GLM analysis indicated that the reduced UA levels in PD were mainly due to sources other than the purine metabolic system, such as exercise, nutritional indices, muscle volume, or adipose tissue. Our results highlight the impairment of purine recycling pathways in PD, as evidenced by the decreased serum hypoxanthine and CSF inosine.

Chronic non-bacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis (CRMO), is a rare autoinflammatory bone disease primarily affecting children and adolescents. This review presents a comprehensive analysis of the intricate relationship between CNO and inflammatory bowel disease (IBD), shedding light on shared pathophysiological mechanisms and clinical management. A thorough literature review was conducted, encompassing 24 case reports involving 40 patients. The demographic distribution of patients revealed a near-equal gender ratio, with a median age of diagnosis at 12 years. The diagnosis patterns showed a higher proportion of CNO as the initial diagnosis, while Crohn's disease was more prevalent than ulcerative colitis. The time interval between the clinical presentations varied, ranging from simultaneous detection to a substantial 15-year gap. Treatment modalities included non-steroidal anti-inflammatory drugs (NSAIDs), steroids, aminosalicylates, and biologic agents, such as infliximab, often overlapping in their use, suggesting shared pathophysiological pathways. Both conditions displayed systemic manifestations, and patients often responded well to immunosuppressive medications. The pathophysiology of CNO involves genetic predisposition, cytokine dysregulation, and osteoclast activation. Dysregulated innate immunity results in immune cell infiltration into bones, causing sterile bone lesions. Notably, emerging evidence hints at a potential link between the microbiome and CNO. In contrast, IBD results from imbalanced mucosal immune responses to the intestinal microbiota. Polymorphisms in the promotor region of IL-10, common cytokines, immune cells, and genetic markers indicate shared immunological and genetic factors between CNO and IBD. Both conditions also involve extraintestinal symptoms. This analysis underscores the need for clinical awareness of the co-occurrence of CNO and IBD, especially among pediatric patients. A deepened understanding of the connections between these seemingly distinct diseases could lead to more effective management and improved patient outcomes.

Background: Hereditary Hemorrhagic Telangiectasia (HHT) is a vascular autosomically inherited rare disease. Epistaxis (nose bleeds) is the most common symptom in HHT, leading to anemia and affecting patient’s quality of life. In addition to epistaxis, gastrointestinal bleeding (GI), more often at older ages, may lead to severe anemia and need for blood transfussions. Thus, finding drugs to control both types of bleeding is a primary necessity in HHT. Methods: A cross-sectional observational study was conducted in a series of 11 HHT patients treated with low tacrolimus doses (0.5-1mg) on an off-label prescription basis. Patients showed refractory bleeding to previous treatments. Epistaxis severity score (ESS) and hemoglobin levels were parameters used to evaluate tacrolimus impact. The occurrence of side effects was also recorded. Results: Tacrolimus was well tolerated in most of the patients, except in 2 which abandoned the treatment. The remaining patients tolerated the treatment, with a general improvement in their health condition. Epistaxis was significantly reduced comparing the ESS before and after treatment. Hemoglobin levels were significantly increased overcoming the anemia in the course of the treatment. Conclusion: Tacrolimus at low doses should be considered as a promising treatment for bleeding derived of epistaxis and GI in HHT.

Sensation seeking (SS) is a psychobiological personality trait characterized by an individual’s propensity to engage in various forms of risk-taking behavior. The Brief Sensation Seeking Scale (BSSS-8) is a widely used instrument for assessing SS that has been translated into several languages. However, only outdated and non-validated questionnaires have been used to measure SS in the Slovenian population. The aim of this study was to translate and psychometrically validate the Slovenian version of the BSSS-8. A total of 363 participants aged between 14 and 65 years completed the translated BSSS-8 and the questionnaire on drug abuse. The scale demonstrated good reliability (Cronbach’s α=0.81) and a unidimensional factorial structure, as revealed by confirmatory factor analysis (CFA). The multigroup CFA showed gender-specific measurement invariance. In the nomological network, SS was positively associated with drug-related variables. The Slovenian version of the BSSS-8 scale is a short and simple instrument to assess SS for research and epidemiological purposes.

Ureteral stricture (US) following ureteroscopic lithotripsy (URSL) has emerged as a serious issue due to the widespread use of laser technology. The management of complex US is challenging. This prospective study evaluated the efficacy of robot-assisted uretero-ureterostomy (RAUU) in addressing US following URSL, and analyzed the pathology of transected ureteral tissues to identify the risk factors for US during URSL. Fourteen patients, with a mean age of 49.8 years, were included in this study. The mean stricture length on radiography was 22.66 ± 7.38 mm. Nine (64.2%) patients had experienced failure with previous interventions, including eight patients who underwent endoscopic incision plus balloon dilation. At an average follow-up of 12.8 months, the overall success rates were 92.9% both clinically and radiographically, without major complications. Pathological findings revealed microcalcifications in 57.1% patients and loss of ureteral mucosa in 28.6% patients. In conclusion, this technique of RAUU via end-to-end anastomosis exhibits promise as a viable option for US following URSL in appropriately selected patients, despite serious pathological changes of the ureter. Migration to the site of ureteral perforation may be the most serious factor contributing to the development of US.

Effective therapeutics for Alzheimer's disease (AD) are in great demand worldwide. In our previous work, we responded to this need by synthesizing novel drug candidates consisting of 4-amino-2,3-polymethylenequinolines conjugated with butylated hydroxytoluene via fixed-length alkylimine or alkylamine linkers (spacers) and studying their bioactivities pertaining to AD treatment. Here, we report significant extensions of these studies, including the use of variable-length spacers and more detailed biological characterizations. Conjugates were potent inhibitors of acetylcholinesterase (AChE, minimum IC50 15.1±0.2 nM) and butyrylcholinesterase (BChE, minimum IC50 5.96±0.58 nM), with weak inhibition of off-target carboxylesterase. Conjugates with alkylamine spacers were more effective cholinesterase inhibitors than alkylimine analogs. Optimal inhibition for AChE was exhibited by cyclohexaquinoline and for BChE by cycloheptaquinoline. Increasing spacer length elevated potency against both cholinesterases. Structure-activity relationships agreed with docking results. Mixed-type reversible AChE inhibition, dual docking to catalytic and peripheral anionic sites, and propidium iodide displacement suggested the potential of hybrids to block AChE-induced β-amyloid (Aβ) aggregation. Hybrids also exhibited inhibition of Aβ self-aggregation in the thioflavin test; those with a hexaquinoline ring and C8 spacer were the most active. Conjugates demonstrated high antioxidant activity in ABTS and FRAP assays as well as inhibition of luminol chemiluminescence and lipid peroxidation in mouse brain homogenates. Quantum-chemical calculations explained antioxidant results. Computed ADMET profiles indicated favorable blood-brain barrier permeability suggesting CNS activity potential. Thus, the conjugates could be considered promising multifunctional agents for potential treatment of AD.

Introduction: Digitalis use in patients with severe heart failure is controversial. We assessed the effects of digitalis therapy on mortality in a large, observational study in recipients of cardiac resynchronization therapy (CRT). Methods: Consecutive patients receiving a CRT-defibrillator in three European tertiary referral centers were enrolled and followed for a median of 28 months. Digitalis use was assessed at the time of CRT implantation. Multivariate Cox-regression model and propensity score matching was used to determine all-cause mortality as primary endpoint. CRT-response (defined as improvement of ≥1 NYHA class), echocardiographic improvement (defined as improvement of LVEF of ≥ 5%), and ICD shocks were assessed as secondary endpoints. Results: The study comprised 552 CRT recipients with standard indications, including 219 patients (40%) treated with digitalis. Compared to patients without digitalis, they had more often atrial fibrillation, poorer LVEF and higher NYHA class (all p ≤ 0.002). Crude analysis of all-cause mortality demonstrated a similar relative risk of death for patients with and without digitalis (HR=1.14; 95% CI 0.88-1.5; p=0.40). After adjustment for independent predictors of mortality, digitalis therapy did not alter the risk for death (adjusted HR=1.04; 95% CI 0.75-1.45; p=0.82). Also, in comparison to 286 propensity score matched patients, mortality was not affected by digitalis intake (propensity adjusted HR=1.11; 95% CI 0.72-1.70; p=0.64). CRT response was predominant in digitalis non-users concerning both improvement of HF symptoms and LVEF (NYHA p<0.01; LVEF p<0.01) while patients on digitalis had more often ventricular tachyarrhythmias requiring ICD shock (p=0.01). Conclusions: Digitalis therapy had no effect on mortality but did negatively affect CRT response and susceptibility to ventricular arrhythmias requiring ICD shock treatment.

Cancer is a complex and devastating disease that has engaged scientists and researchers for decades. Despite tremendous efforts, previous hypotheses about cancer development have not achieved significant breakthroughs. Evolutionary Cancer Cell Biology (ECCB) is a novel and emerging branch of oncological science that provides an evolutionary perspective on the origin of cancer. It reveals that the cancer genome evolved hundreds of millions of years ago, long before multicellular organisms such as metazoans and humans emerged. ECCB aims to unify all evolutionary insights, hypotheses, and theories into a cohesive framework. It investigates the intricate relationship between cancer genomics and ancient pre-metazoan genes that emerge when normal cells transform into cancer cells. It challenges the conventional wisdom of cancer research by suggesting that cancer could arise through intrinsic cellular mechanisms without genetic alterations and mutations. Furthermore, it postulates that somatic mutations are only secondary, downstream events in the process of oncogenesis.

Background: Computed tomography examinations have produced high radiation doses to patients, especially the CT brain. This study aimed to optimize the radiation dose and image quality in adult CT brain protocol. Materials and Methods: Images were acquired by Catphan 700 phantom. Radiation doses were recorded as CTDIvol and dose length product (DLP). CT brain protocols were optimized by varying parameters such as kVp, mAs, signal-to-noise ratio (SNR) level, and Clearview iterative reconstruction (IR). Image quality were also evaluataion by The AutoQA Plus software. Results: CT Number accuracy and linearity had a robust positive correlation with the linear attenuation coefficient (µ) and showed more inaccurate CT numbers when using 80 kVp. MTF showed a higher value in 100 and 120 kVp protocols, while high contrast spatial resolution showed a higher value in 80 and 100 kVp protocols. Low contrast detectability and CNR tended to increase when using high mAs, SNR and Clearview IR protocol. Noise decreased when using a high radiation dose and a high percentage of Clearview IR. CTDIvol and DLP were increased with increasing kVp, mAs, and SNR levels, while the increasing percentage of Clearview did not affect the radiation dose. Conclusion: Optimized protocols, including radiation dose and image quality, should be evaluated to preserve diagnostic capability. The recommended parameter settings include kVp set between 100-120 kVp, mAs ranging from 200-300 mAs, SNR level within the range of 0.7-1.0, and an iterative reconstruction value of 30% Clearview to 60% or higher.

This mini-review examines the complex relationship between the gut microbiota and human health, with a special focus on its role in conditions such as inflammatory bowel disease (IBD) and cardiovascular disease (CVD). It explores how dietary patterns can affect the composition of the gut microbiota, thus contributing to the development of various diseases. The gut microbiota is crucial in the production of metabolites such as trimethylamine N-oxide (TMAO), which play a significant role in the development of both IBD and CVD. High levels of TMAO and other metabolites, such as phenylacetylglutamine, have been linked to an increased risk of CVD. The review highlights the potential of dietary interventions and therapies designed to modulate the gut microbiota in reducing these risks. Following a Mediterranean diet may offer cardiovascular protection, emphasizing the need for further research into the molecular mechanisms of diet-related changes in the microbiota.

Background High Mobility Group Box-1 (HMGB-1) is implicated in the pathogenesis of thrombosis and cancer. In the present study, we aimed to evaluate its potential role as a diagnostic biomarker of portal vein thrombosis (PVT) among patients with hepatocellular carcinoma (HCC). Methods The study population included N=100 prospectively recruited patients with a novel diagnosis of HCC. We compared circulating HMGB-1 levels between 34 healthy controls, HCC patients with PVT (N=22), and HCC patients without PVT (N=78). Results HCC patients without PVT showed significantly higher median HMGB-1 serum levels (8.2 [5.5-13.1] ng/ml) than those observed in the case of HCC with PVT (5.5 [4.4-8.5] ng/ml; p=0.012) and in healthy controls (4.1 [3.1-8.2] ng/ml; p&lt;0.001). Among HCC patients, at univariate analysis, the presence of PVT was associated with higher median age (p=0.036), larger major cancer node diameter (p&lt;0.001), and lower HMGB-1 serum level (p=0.012). At multivariate analysis, the presence of PVT maintained a positive association with major node diameter p=0.001) and an inverse association with serum HMGB-1 levels (p=0.003). Conclusions These findings indicate that serum HMGB-1 bears an inverse association with PVT complicating HCC at the time of diagnosis and suggest that serum HMGB-1 depletion may mark PVT development in cirrhotic patients with HCC.

Published in July 2018, TAILORx aimed to establish non-inferiority of endocrine therapy (ET) compared to addition of chemotherapy (CHT-ET) in hormone receptor positive, human epidermal receptor 2 negative (HR+/HER2-) breast cancer (BC) patients with a 21-gene intermediate (11-25) recurrence score (RS). While this hypothesis proved correct, the study did show benefit of addition of chemotherapy (CHT) in a subgroup of women under 50 years of age, and particularly in the RS 16-25. The aim of this present study was to look at how TAILORx findings, including changes in RS categories, impacted CHT implementation at one oncologic center in Basel, Switzerland, and to identify main factors leading to these changes. Methods: We conducted a retrospective study on HR+/HER2-, BC patients who underwent 21-gene genomic testing between 2010-2021, at our center. Patients with metastatic disease were not included. We identified 326 eligible patients, of which 165 had a BC diagnosis before TAILORx (cohort A) and 161 after TAILORx publication (cohort B). Results: Demographic and tumor characteristics were similar in the two cohorts, although cohort B included significantly more women under the age of 50 when compared to A (34% vs. 24%, p<0.001). Median age and mean RS results were comparable 59 (IQR 16) in A and 58 (IQR 19) years in B and 17.72 (SD9.59) in A and 17.89 (SD9.53) in B, respectively. Patients in cohort A were slightly more overweight when compared to B (55% vs. 40% respectively, p<0.001). Most patients had stage II tumors of NST histologic type. Tumors in cohort B had higher Ki-67 than cohort A (39% vs. 32%, p=0.010). When compared based on manufacturer’s and based on TAILORx thresholds there were no significant differences in RS distribution. However, changes in score category led to shifts in patient population distribution, leading to a 40% drop in the low RS (from 60% to 20%), a doubling in the intermediate RS (from 30% to 60%) and an increase of 5% in the high RS (from 8-10% to 15%). Most patients had conservative surgery, adjuvant radiotherapy (RT) and ET. Overall CHT recommendation and application did not differ significantly in B vs. A. There was a reduction of 1% in the intermediate RS (11-25) and an increase of 13% CHT-ET application in the high RS (>26) category. In cohort B we noticed an increase in CHT-ET application among women <50 years old (by 12.5%), in lobular carcinomas (by 10%), grade 3 tumors (by 2%), node positive BC (by 3%) and node negative (by 2%). Tumor board recommendation for CHT dropped by 1% in the post TAILORx era, with a notable reduction of 5% in the intermediate RS (11-25) category. However, overall CHT administration rate was 19% in cohort A and 22% in B (p=0.763). Tumor Board recommended CHT for 90% of the BC patients that would have otherwise been assigned to CHT according to new RS guidelines in A and for 85% in B, showing a trend for undertreatment. Logistic regression analysis showed significance of age in both cohort A (OR 1.05, 95% CI 1.01-1.11, p=0.03) and cohort B (OR 0.89, 95% CI 0.84-0.94), p<0.001), and of nodal status in both cohort A (=R 3.32 95% CI 1.09-10-06, p=0.034) and cohort B (OR 3.31, 95% CI 1.29-8.53, p=0.013), while intermediate and high RS seem to be more relevant in cohort A (OR 0.12, 95% CI 0.03-0.43, p=0.01 and OR 0.04, 95% CI 0.01-0.21, p<0.01). Overall logistic regression analysis showed relevance of age (OR 0.93, 95% CI 0.08-0.97, p=0.001), pN (OR 4.77, 95% CI 2.03-11.22, p<0.001) and RS categories (RS 11-25: OR 0.02, 95% CI 0.01-0.07, p<0.001; RS>26: OR 617.93, 95% CI 57.97-6587.16, p<0.001). Conclusion: Our findings are similar to those reported across several studies: while tumor board recommendation for CHT decreases in the intermediate RS category, there is an increase being reported in the high RS category, leading to overall minor changes in CHT application. Administration of CHT-ET seems to be increasing among younger women, with unfavorable histo-pathological factors, such as lobular carcinoma and G3 histologic grade. Before TAILORx there is a tendency for undertreatment (-10%), especially among older BC patients, which seems to be maintained and even deepened (-15%) in the post TAILORx era, pointing to a personalized decision-making approach among Swiss oncologists.

Abstract Background: Massive resection of the small intestine leading to short bowel syndrome (SBS) deprives organism of many immunocompetent cells concentrated in gut associated lymphoid tissue- the largest immune organ in humans. We have aimed to access the influence of bowel resection on adaptive immunity in children, basing on peripheral lymphocyte subsets and serum immunoglobulins. Methods: 15 children, who underwent bowel resection in the first month of life and required further home parenteral nutrition were enrolled into the study.. Based on flow cytometry the following subsets of lymphocytes were evaluated: T, B, NK, CD4+, C8+and activated T cells. Results: Significantly statistical differences were found for the rates of lymphocytes B, T, CD8 + and NK cells. Absolute count of NK cells was lower in SBS group than in the control group. Absolute counts of lymphocytes, lymphocytes B, T, CD4+ and percentages of lymphocytes CD4+, and activated T cells inversely correlated with the time after resection. Conclusions: Children with SBS do not present with clinical signs of immunodeficiency as well as deficits in peripheral lymphocyte subsets and serum immunoglobulins. The tendency of the lymphocyte subpopulations to decrease over time after resection points out the necessity for longer follow- up.

The ATP-binding cassette (ABC) transporter ABCG2 is a significant urate transporter with a high capacity, and it plays a crucial role in the development of hyperuricemia and gout. Therefore, it has the potential to be targeted for therapeutic interventions. Cortex Fraxini, a traditional Chinese medicine (TCM), has been found to possess anti-hyperuricemia properties. However, the specific constituents of Cortex Fraxini responsible for this effect are still unknown, particularly the compound that is responsible for reducing uric acid levels in vivo. In this study, we propose a target screening protocol utilizing bio-affinity ultrafiltration mass spectrometry (BA-UF-MS) to expediently ascertain ABCG2 ligands from the plasma of rats administered with Cortex Fraxini. Our screening protocol successfully identified fraxin as a potential ligand that interacts with ABCG2 when it functions as the targeted protein. Subsequent investigations substantiated fraxin as an activator of ABCG2. These findings imply that fraxin exhibits promise as a drug candidate for the treatment of hyperuricemia. Furthermore, the utilization of BA-UF-MS demonstrates its efficacy as a valuable methodology for identifying hit compounds that exhibit binding affinity towards ABCG2 within TCMs.

Background: Patients with infectious complications related to the presence of cardiac implantable electronic devices (CIED) constitute a heterogeneous group, including local pocket infection (PI) and lead related infectious endocarditis (LRIE). The diagnosis of CIED-related infection is often difficult and requires complex imaging and microbiological tests. The aim of the current study was to evaluate the usefulness of new simple hematological parameters in detecting infectious complications in patients with CIED and assessing their extent. Methods: The retrospective analysis of clinical data of 2909 patients (36.37% with CIED-related infections), undergoing transvenous lead extraction (TLE) procedures in three high-volume centres in the years 2006-2020, was conducted. The sensitivity and specificity of new hematological markers were evaluated: the neutrophil to lymphocyte ratio (NLR), neutrophil to platelet ratio (NPR), and lymphocyte to platelet ratio (LPR) in the diagnosis of infectious complications, assessment of the spread of the infectious process and differentiation of additional structures related to the presence of leads. Results: In patients with CIED infections, compared to the non-infectious group, high inflammatory parameters were confirmed, and the highest specificity of the new markers in detecting the infectious process was demonstrated. (79.47% for NPR and 72.82% for NLR). Analysis of laboratory parameters in infectious and non-infectious patients with the presence of additional lead-related masses showed the highest specificity of NPR (82,78%) in predicting the diagnosis of vegetation. Comparison of laboratory parameters in patients with LRIE and PI showed higher NLR % (4.24 vs 2.56; p<0.001, area under curve (AUC) in a receiver operating characteristic (ROC) curve: 0.67 and 0.78 respectively) and higher NPR (0.03 vs 0.02; p<0.001; AUC: 0,51 and 0,55) in patients with LRIE. The highest sensitivity in the detection of coexistence LRIE with PI has been demonstrated for NLR (87.33%). Conclusions: Novel hematological markers may be helpful in the recognition of the inflammatory process in patients with CIED, differentiation of vegetation and vegetation-like masses, and the extent of infection in patients with PI.

Perilla frutense var. acuta (Lamiaceae) has been used to treat indigestion, asthma, and allergies in traditional medicine. In this study, luteolin 7-O-diglucuronide (1), apigenin 7-O-diglucuronide (2), and rosmarinic acid (3) were isolated from the leaves of P. frutescens var. acuta. Various approaches were performed to investigate the anti-inflammatory activity of the isolated compounds (1-3) and their working mechanisms. In silico docking simulation demonstrated that 1-3 would work as a PPAR-α/δ/γ agonist, and in vitro PPAR-α/δ/γ transcriptional assay showed that the Perilla extract and 3 increased PPAR-α luciferase activity [1.71 and 1.61 times of the control (PPAR-α + PPRE, p < 0.001)]. In the NF-κB luciferase assay, 1 suppressed NF-κB activity the most (56.83 % at 5 µM; 74.96 % at 10 µM; 79.86 % at 50 µM). In addition, 1 and 2 inhibited the mRNA expression of NF-κB target genes, including Il6, Mcp1, and Tnfa, at 50 µM, and 3 suppressed the genes at the mRNA level in a dose-dependent manner. We report that 1 and 2 exert anti-inflammatory effects through NF-κB inhibition, and PPAR-α/NF-κB signaling pathway is related to the anti-inflammatory activity of 3.

Background The evolution of treatment patterns in neovascular age-related macular degeneration (nAMD) warrants investigation into the impact of patients’ adherence to anti-vascular endothelial growth factor (VEGF) treatment on visual outcomes. This retrospective, non-randomized, non-comparative study aimed to investigate real-world adherence to anti-VEGF treatment. Methods Patients (eyes) (≥ 50 years) with a diagnosis of nAMD who had a first injection of aflibercept or ranibizumab between January 2016 and December 2018 and 12 months of follow-up were included. Visual acuity (VA; logarithm of the minimum angle of resolution letters) and duration of injection intervals were recorded. Adherence was defined as < 20% of visits deviating from the schedule by ≥ 14 days. Results Overall, 133 patient eyes were included: 129 adherent, 4 non-adherent. Mean (± standard deviation) baseline VA was 57.0 (± 23.6) and 53.8 (± 35.3) letters in adherent and non-adherent patient eyes, respectively. Mean change in VA by month 12 was higher in adherent (6.3 letters) than non-adherent patient eyes (−11 letters). In non-adherent patient eyes, no improvement in VA was recorded following completion of the loading period (month 3). Compared with the previous visit, adherent visits were associated with a mean increase in VA of 0.67 letters and non-adherent visits with a decrease of 2.30 letters. Conclusions These results emphasize the importance of adherence to appropriate dosing regimens to optimize visual outcomes in patients with nAMD.

Bioactive peptides are promising cosmetic active ingredients that can improve skin health and appearance. They exhibit a broad spectrum of activity, including anti–ageing, antioxidant, antimicrobial and anti–inflammatory. The aim of this study was to develop a safe, stable and efficacious environmentaly friendly ("green") emulsion using milk protein hydrolysate as a model active ingredient. Potential emulsions were formulated with biodegradable emollients, stabilised with a naturally-derived mixed emulsifier and prepared by cold process. They were evaluated for rheological behavior (continuous rotation and oscillation tests), physical stability (dynamic mechanical thermal analysis - DMTA test) and texture profiles, as well as for cytotoxic, antioxidant and antimicrobial effects. Rheological characterization revealed shear-thinning flow behaviour with yield point from continuous rotation tests and predominantly elastic character from oscillation (amplitude and frequency sweep) tests, with small structural change detected in the DMTA test. These results implied satisfactory rheological properties and good stability. Texture analysis revealed acceptable spreadability and substantivity of the emulsions. The protein hydrolysate showed antioxidant activity. The developed emulsions showed low antibacterial activity against selected microorganisms, but this was due to the action of preservatives, not peptides. All potential emulsions showed desirable safety profile. The results obtained provide the basis for the next stage of formulation development, i.e. in vivo efficacy tests.

Introduction: Endoscopic biliary stenting is a widely utilized procedure in the realm of interventional gastroenterology, primarily employing plastic stents for short-term biliary drainage. This case series endeavours to investigate the occurrence and ensuing clinical ramifications of forgotten or retained biliary stents. Methods: Carried out over an 8-month duration at King George Hospital in Visakhapatnam, this case series encompasses 12 patients diagnosed with forgotten biliary stents. Diagnostic confirmation was established through a combination of X-ray, abdominal ultrasound, and magnetic resonance cholangiopancreatography (MRCP). Four patients experienced complications such as fractured distal pigtails and obstructed stents, thwarting retrieval efforts via endoscopic retrograde cholangiopancreatography (ERCP) and cholangioscopy. Results: This case series featured 12 patients with a median age of 48 years (range: 18-76), comprising 7 females (58.3%) and 5 males (41.7%). The primary indication for initial stent placement was choledocholithiasis in 10 instances (83.3%), while benign biliary strictures accounted for 3 cases (25%). On average, patients presented 31.3 months post-initial stenting, primarily manifesting cholangitis symptoms (83.3%). ERCP succeeded in stent removal in 8 cases (66.6%), while the remaining cases necessitated advanced procedures such as cholangioscopy, with two patients being referred for surgical intervention. It is noteworthy that there were no instances of mortality. Conclusion: This case series, conducted against the backdrop of the COVID-19 pandemic, highlights an increased prevalence of neglected plastic biliary stents. The principal complication encountered was cholangitis, often coexisting with common bile duct (CBD) stones. Standard ERCP techniques demonstrated reduced efficacy in instances characterized by fractured, obstructed, or displaced stents, necessitating the exploration of alternative strategies like cholangioscopy or surgical intervention. This compilation of cases underscores the pressing imperative for prompt stent retrieval and the enhancement of management protocols to proactively mitigate the potential for complications.

Atrial fibrillation (AF) is the most common cardiac arrhythmia encountered in clinical practice, affecting millions of individuals worldwide. The management of AF presents significant challenges due to its complex nature and diverse patient profiles. In recent years, the integration of artificial intelligence (AI) and machine learning technologies has emerged as a promising approach to enhance various aspects of AF management. This comprehensive review aims to explore the evolving role of AI in AF management, with a focus on its potential applications in diagnosis, risk prediction, treatment selection, and patient monitoring. Real academic references were employed to provide evidence-based insights into the impact of AI on AF management.

Food Neophobia (FN), defined as the reluctance to eat new or unfamiliar foods, mainly concerns fruit, vegetables, and legumes, typical of the Mediterranean Diet (MD). Considering these premises, this study aimed to clarify the relationship between FN and AMD in a sample of Italian children and their association with some socio-demographic factors and children's nutritional status. A sample of 288 children aged 3-11 years, participated to an assessment carried out with a questionnaire evaluating FN and AMD, respectively with Child Food Neophobia Scale (CFNS) and the KIDMED Test. Most of the sample showed an intermediate (67.3%) or high level of FN (18.1%) with high rates among 6-11 years old children (63.9%) and especially in only-child (50%). The AMD was mostly low (29.5%) or medium (54.8%) and reached lower levels among higher neophobic children (51.9%; p value &lt; 0.05). Present results confirm the study hypothesis that FN is a driver of MD abandonment and show the positive effects on children's eating habits of having siblings. Finally, this study proves the relevance of adopting effective feeding strategies against FN to avoid its maintenance in adulthood and detrimental effects on future overall health and well-being.

Introduction. This retrospective study aimed to compare the risk factors for vascular calcification (VC) between pre-hemodialysis (HD) and prevalent HD adult patients while investigating associations with calcification biomarkers. Methods. Baseline data from 30 pre-HD and 85 HD patients were analyzed, including iPTH, vitamin D, FGF23, fetuinA, sclerostin, and VC scores (Adragao method). Multivariable linear regression identified VC predictors. Results: The prevalence of VC was similar in both groups, but HD patients had more pronounced VC scores ≥6. Pre-HD patients were older, with higher prevalence of Balkan endemic nephropathy, hypertension, and less frequent use of calcium phosphate binders. Both groups exhibited similar patterns of hyperphosphatemia, low vitamin D, and iPTH levels. In HD group normal phosphate was significantly common in patients with VC, whereas hyperphosphatemia was significantly common in patients without VC. Fetuin-A levels were higher in pre-HD patients, while FGF23 was elevated in HD patients. In pre-HD patients, male gender was associated with reduced VC risk, while in HD patients, malignancies and serum phosphate levels were negative VC predictors. Conclusion: Effective monitoring and tailored treatment of VC in CKD are still focused on phosphate regulation. Besides, mineral disturbances, hormones and biomarkers regulation, and patient-specific variables need to be considered.

Vitamin D deficiency and insufficiency are highly prevalent in CKD affecting over 80% of hemodialysis (HD) patients and require therapeutic intervention. Nephrological societies suggest the administration of cholecalciferol according to the guidelines for the general population. The aim of the observational study was to evaluate the efficacy and safety of the therapy with a high dose of cholecalciferol in HD patients with 25(OH)D deficiency and insufficiency to reach the target serum 25(OH)D level &gt; 30 ng/mL. 22 patients (16 M), with an average age of 72.5 ± 13.03 years and 25(OH)D concentration of 13.05 (9.00–17.90) ng/mL were administered cholecalciferol at a therapeutic dose of 70,000 IU/week (20,000 IU + 20,000 IU + 30,000 IU, immediately after each dialysis session). All patients achieved the target value &gt;30 ng/mL, with a mean time of 2.86 ± 1.87 weeks. In the first week, the target level of 25(OH)D (100%) was reached by 2 patients (9.09%), in the second week – by 15 patients (68.18%), in the fourth week – by 18 patients (81.18%) and in the ninth week by all 22 patients (100%). A significant increase in 1,25(OH)2D levels was observed during the study, however, only 2 patients (9.09%) achieved a concentration of 1,25(OH)2D above 25 ng/mL – the lower limit of the reference range. The intact PTH concentrations remained unchanged during the observation period. No episodes of hypercalcemia, and one new episode of hyperphosphatemia were observed. In conclusion, our study showed that the administration of a high therapeutic dose of cholecalciferol allowed for a quick, effective, and safe leveling of 25(OH)D concentration in HD patients.

Mesothelioma is a cancer arising from mesothelial cells lining the thoracic (pleura) or the abdominal (peritoneum) cavities, and more rarely from transformed mesothelial cells of pericardium or tunica vaginalis testis. The development of mesothelioma has been related to the exposure to carcinogenic mineral fibers, mainly asbestos. Malignant mesothelioma is an aggressive disease with diffuse nature, low median survival, and prolonged latency presenting difficulty in prognosis, diagnosis, and treatment. We here review all these aspects to underline the progress being made in investigation and to emphasise how much work remains to be done to improve prognosis and treatment.

An array of diverse processes and factors have been linked to the pathoetiology and pathophysiology of Parkinson’s disease (PD), including systemic CNS factors. This article reviews some of the many processes and factors linked to the emergence and progression of PD that culminates in the loss of substantia nigra pars compacts (SNpc) in PD patients. It is proposed that SNpc astrocytes may be a key hub, with numerous systemic and CNS factors acting to suppress the astrocyte tryptophan-melatonin pathway, leading to a loss of astrocyte melatonin and lactate for SNpc dopamine neurons. Consequently, dopamine neurons show an increase in α-synuclein, oxidative stress and suboptimal mitochondrial function, partly due to the loss of melatonin induced PTEN-associated kinase (PINK)1/parkin and mitophagy. This leads to an increase in the major histocompatibility (MHC)-1 and the chemoattraction of CD8+ T cells that destroy SNpc dopamine neurons in an ‘autoimmune’/’immune-mediated’ manner. The upstream processes driving the end-point ‘chaos’ of SNpc dopamine neuron loss are proposed to be driven by the suppression of night-time pineal melatonin, gut microbiome derived butyrate and possibly bcl2-associated athanogene (BAG)-1, which all act to suppress the glucocorticoid receptor (GR) translocation to the nucleus in all systemic and CNS cells, thereby potentiating the effects of the rising levels of cortisol over the night and accelerated rise in the course of the cortisol awakening response (CAR). The potentiation of cortisol effects at the GR has consequences for the homeostatic regulation of the diverse array of systemic and CNS microenvironments, as well as a distinct regulation of different immune and glia cells. The morning CAR is classically proposed to ‘prepare the body for the coming day’. However, the differential regulation of the GR over the circadian rhythm at night would indicate that such preparation for the coming day may be powerfully determined by night-time factors and processes. The article integrates this systemic, night-time pathoetiology with the ‘immune-mediated’ processes that ultimately drive SNpc dopamine neuron loss. This has a number of novel future research and treatment implications.

Carbohydrates such as fructooligosaccharides (FOS) are associated with improved gastrointestinal health and prevention of excess body fat. We evaluated the long-term effects of high amounts of FOS on metabolic parameters, non-alcoholic fatty liver disease (NAFLD) and short-chain fatty acids (SCFA). Sixty C57BL/6 mice received diets for four months: control (C), normolipid rich in fiber (F), normolipid supplemented with FOS (FOS), high fat (HL), high fat with high fiber (HLF) and high fat with FOS (HLFOS). We analyzed: animal weight; body composition; food intake; fasting blood glucose; serum and liver lipid profile; liver and intestinal histologies; malondialdehyde (MDA), hepatic retinol and α-tocopherol; SCFA in the feces. Supplementation with FOS in a high-fat diet promoted less body weight gain and reduced liver and retroperitoneal adipose tissue weights compared to HL and HF. FOS prevented NASH and decreased alanine aminotransferase and serum cholesterol levels in experimental animal models of obesity and metabolic syndrome (MS). There was found statistical differences in the dosages of the three main SCFAs in feces (acetic, isobutyric and isovaleric acids). Long-term supplementation with high doses of FOS was effective in reducing weight, adiposity, NAFLD and serum cholesterol in C57BL mice with obesity and MS induced by a high-fat diet.

Consideration of the individual bone characteristics of the wrist plays a key role in well-functioning biomedical devices and successful surgical procedures. Although geometric differences and individual bone sizes have been analyzed in the literature, detailed morphologic descriptions and correlations covering the entire wrist reported in a clinical context are lacking. This study aimed to perform a comprehensive and automatic analysis of wrist morphology using the freely available “Open Source Carpal Database” (OSCD). We quantified the dimensions of each of the individual carpal bones and their combination. These dimensions were extracted in n=117 datasets of the wrist of the OSCD in anatomical directions and analyzed using descriptive statics and correlation analysis to investigate morphological characteristics under gender-specific aspects. We found that there exist statistical differences between genders, and we concluded that gender specificity is an important variable affecting the utilization of biomedical device designs and clinical treatment.

Resuscitation is one of the most stressful tasks in emergency medicine. The participation of medical professionals in this procedure can have specific effects on them. In the research, we wanted to find out what these effects are. A qualitative approach by conducting semi-structured interviews was used, and thematic data analysis of the recorded interviews was done. The collected data were transcribed verbatim with no corrections to the audio recordings. The computer program ATLAS.ti 22 was used for qualitative data analysis. Eleven male registered nurses were interviewed, with an average of 18.5 years of experience working in a prehospital environment (max. 32/min. 9). A total of 404 minutes of recordings were analyzed and 789 codes were found, which were combined into 36 patterns, and 11 themes. As the most stressful situa-tions, the interviewees pointed out the resuscitation of a child, familiar persons, conflicts with the environment, conflicts within the resuscitation team, non-functioning or insufficient equipment, complications during resuscitation, and resuscitating a person only for exercise. As positive effects, the interviewees cited successful resuscitations or their awareness that, despite the unsuccessful resuscitation, they did everything they could. Participation in these interven-tions has a specific positive or negative impact on the performers. The interviewees shared the opinion that they can cope effectively with resuscitation's adverse or stressful effects. Yet, de-spite everything, they allow the possibility of subconscious influences of this intervention on them.

Osteoporosis, often linked to increased osteoclast activity due to menopause or aging, was the focus. In this study, the inhibitory effects of Salicornia europaea L. (SE) water extract of desalted SE (WSE) were investigated on osteoclast differentiation and bone loss in ovariectomized mice. The findings revealed that WSE effectively inhibited RANKL-induced osteoclast differentiation, as evidenced by TRAP staining, and also suppressed bone resorption and F-actin ring formation in a dose-dependent manner. Gene expressions related to osteoclast differentiation, including NFATc1, TRAP, cathepsin K, and DC-STAMP, were downregulated by WSE. Oral administration of WSE improved bone density and structural parameters in ovariectomized mice. Dicaffeoyl quinic acids (DCQAs) and saponins in WSE were detected, with 3,4-, 3,5-, and 4,5-DCQA isolated and identified. All tested DCQAs, including the aforementioned types, inhibited osteoclast differentiation, bone resorption, and the expression of osteoclast-related genes. Furthermore, WSE and DCQAs reduced ROS production mediated by RANKL. These results indicate the potential of WSE and its components, DCQA, as preventive or therapeutic agents against osteoporosis and related conditions.

.Celiac disease (CeD) is a chronic, autoimmune disorder triggered by the ingestion of gluten, affecting around 1% of the global population. It is a multifactorial disease involving both genetics and environ-mental factors. Nowadays, the only available treatment for CeD is a life-long gluten-free diet (GFD), which can cause a significant burden for patients, since symptoms and mucosal injury can persist de-spite apparent compliance with a GFD. That could also lead to psychological consequences and affect the quality of life of these patients. Thankfully, recent advances in understanding the pathogenesis of CeD and the availability of various targets have made it feasible to explore pharmaceutical treatments specific to CeD. Recently, the FDA has highlighted the unmet needs of adult patients on GFD who expe-rience ongoing symptoms attributed to CeD and also show persistent duodenal villous atrophy. This re-view will outline the limitations of a GFD, describe the targets of potential novel treatment of CeD and provide an overview of the primary clinical trials involving oral and injectable agents for a non-dietary treatment of CeD.

(1) Background: Spontaneous isolated intramural hematoma of the superior mesenteric artery (SIHSMA) is a rare entity often considered as a subset of spontaneous isolated dissection of the superior mesenteric artery (SIDSMA). It is characterized by a completely thrombosed false lumen with or without ulcer-like projection with computed tomography (CT) imaging. The recent literature describes few reports with a relatively short-term follow-up. The natural course, prognosis, and treatment options for SIHSMA still lack consensus. We present two cases of acute abdominal pain in a young man due to IMH of the superior mesenteric artery with an extensive literature review. (2) Case report: A 46-year-old male patient was submitted to an urgent CTA for acute abdominal pain, showing the presence of an isolated dissection of the superior mesenteric artery, determining significant stenosis of the vessel with collateral vessel patency. The patient referred to a recent COVID-19 infection, whose course was paucisymptomatic. He was treated conservatively with antiplatelet therapy and corticosteroid treatments, and, after a few days, the symptomatology completely regressed; also, 2-month- control CTA showed the complete IMH regression and the absence of any signs of residual stenosis. The second patient is a 61-year-old male patient who was submitted to an urgent CTA for acute abdominal pain, showing the presence of an isolated dissection of the superior mesenteric artery, not determining significant vessel stenosis. He was treated conservatively with antiplatelet therapy and corticosteroid treatment, and after a few days, the symptomatology completely regressed, and the radiological control showed a complete dissection regression. (3) Conclusion: SISHSMA is a rare entity of vascular pathology, and conservative management represents the best medical strategy. We propose corticosteroid treatment as one of the most appropriate tools in the conservative treatment of SISHSMA.

The HSP70 and HSP90 family members belong to molecular chaperones that exhibit protective functions during the cellular response to stressful agents. We investigated whether the exposure of rats to chronic mild stress (CMS), a validated model of depression, affects the expression of HSP70 and HSP90 in the prefrontal cortex (PFC), hippocampus (HIP) and thalamus (Thal). Male Wistar rats were exposed to CMS for 3 or 8 weeks. The antidepressant imipramine (IMI, 10 mg/kg, i.p., daily) was introduced in the last five weeks of the long-term CMS procedure. Depressive-like behavior was verified by the sucrose consumption test. The expression of mRNA and protein was quantified by real-time PCR and Western blot, respectively. In the 8-week CMS model, stress alone elevated HSP72 and HSP90B mRNA expression in the HIP. HSP72 mRNA was increased in the PFC and HIP of rats not responding to IMI treatment vs. IMI responders. The CMS exposure increased HSP72 protein expression in the cytosolic fraction of the PFC and HIP, and this effect was diminished by IMI treatment. Our results suggest that elevated levels of HSP72 may serve as an important indicator of neuronal stress reactions accompanying depression pathology and could be a potential target for antidepressant strategy.

Recent research has unveiled intriguing insights suggesting that the body's immune system may be implicated in Parkinson's disease (PD) development. Studies have observed disparities in pro-inflammatory and anti-inflammatory markers between PD patients and healthy individuals. This finding underscores the potential influence of immune system dysfunction in the genesis of this condition. A dysfunctional immune system can serve as a primary catalyst for systemic in-flammation in the body, which may contribute to the emergence of various brain disorders. The identification of several genes associated with PD, as well as their connection to neuroinflamma-tion, raises the likelihood of disease susceptibility. Moreover, advancing age and mitochondrial dysfunction can weaken the immune system, potentially implicating them in the onset of the dis-ease, particularly among older individuals. Compromised integrity of the blood-brain barrier could facilitate the immune system's access to brain tissue. This exposure may lead to encounters with native antigens or infections, potentially triggering an autoimmune response. Furthermore, there is mounting evidence supporting the notion that gut dysbiosis might represent an initial trigger for brain inflammation, ultimately promoting neurodegeneration. In this comprehensive review, we will delve into the numerous hypotheses surrounding the role of both innate and adaptive immunity in PD.

Presenting a case report about an occurrence of duodeno-duodenal intussusception in a 17-year-old female patient. Intussusception is typically observed in children. The patient has a history of recurrent pain and vomiting for four days. During the examination tenderness in the epigastric area worsened when the legs were elevated. An initial X-ray of the abdomen was done and the findings were normal. Subsequent ultrasound and abdominal CECT scans of the abdomen revealed intussusception involving the 2^nd, 3^rd, and 4^th part of the duodenum ampulla of Vater and pancreas without any identifiable cause for this condition. There was no abnormal thickening of the wall. This case shows how using radiological imaging and surgical management helps to prevent severe complications in cases like duodeno-duodenal intussusception in adults.

Definitive surgical resection is the preferred treatment for early-stage non-small-cell lung cancer (NSCLC). Research into genetic alterations, including epidermal growth factor receptor (EGFR) mutation, in early stage NSCLC remains insufficient. Here, we investigated the prevalence of genetic alterations in early-stage NSCLC and the association between EGFR mutation and recurrence after complete resection. Between January 2019 and December 2021, 659 patients with NSCLC who underwent curative surgical resection at a single regional cancer center were recruited. We compared the clinical and pathological data between the recurrence and non-recurrence groups. Multivariate logistic regression was used to predict the risk factors for recurrence. Among the 659 enrolled cases, the most common histology was adenocarcinoma (74.5%), followed by squamous cell carcinoma (21.7%). The prevalence of EGFR mutation was 43% (194/451). Among them, L858R point mutation and exon 19 deletion was 52.3% and 42%, respectively. ALK rearrangement was found at 5.7% (26/453), and ROS1 fusion was found at 1.6% (7/441). The recurrence rate of the entire population was 19.7%. In multivariate analysis, the presence of EGFR mutation, stage II or III (vs. stage I), and pathologic subtype (presence of solid type) were associated with recurrence. Among the recurred group, 86.5% of the patients with EGFR mutation experienced distant recurrence compared to only 66.7% of wild-type (p = 0.016), with no significant difference in median disease-free survival (p = 0.983). In conclusion, the prevalence of EGFR mutation, ALK rearrangement, and ROS1 fusion was 43.0%, 5.7%, and 1.6%, respectively in patients with early-stage NSCLC who underwent curative resection. Along with stage II/III and solid pathologic subtype, EGFR mutation was an independent risk factor for recurrence. In the recurrence group, the rate of distant metastasis was higher in patients with EGFR mutation than in those with wild-type.

Gout is at least 3 times more prevalent in men than in women. However, concurrent with rising total gout prevalence, complex factors, including comorbidities, diet and lifestyle, and aging, have promoted higher gout prevalence in females. This narrative review focuses on summarizing recent developments in the landscape of gout in women, and mechanisms involved. New knowledge on sex hormone effects on both urate-excreting and urate-reabsorbing transporters, and higher hypertension and chronic kidney disease prevalence in women compared to men, may help explain why gout incidence rises robustly after menopause in women to approach that in men. Racial and ethnic factors, risk profiles based on heritable genetic polymorphisms of urate transporters, and diet, body mass index, and lifestyle factors differ according to sex. In addition, sex differences in clinical phenotypes and outcomes of gout and non-gout illnesses include more frequent comorbidities, more pain and disability during gout flare, different perceptions of disease burden, and more frequent severe cutaneous hypersensitivity reaction to allopurinol in women. Significantly, women with gout also have poorer COVID-19 outcomes than do men. Collectively, such findings support the potential clinical benefits of tailoring gout and hyperuricemia treatment according to sex.

This comprehensive review delves into the intricate relationship between Sodium-GlucoseCo-Transporter 2 (SGLT2) inhibitors and AF, highlighting the multifaceted actions of thesedrugs and their significant cardiovascular benefits. Mechanisms: SGLT2 inhibitors inducesubstantial hemodynamic changes, impacting blood pressure, adipose tissue function, andinflammation. They enhance glycemic control while potentially reducing oxidative stress andinflammation, and they modulate atrial electrophysiology, collectively contributing to the reductionof AF risk. Clinical Evidence: This review synthesizes a wealth of clinical evidence,drawing from observational studies and randomized controlled trials, consistently demonstratinga correlation between SGLT2 inhibitors, particularly dapagliflozin and empagliflozin, anda decreased risk of AF. This protective effect is most pronounced in patients with type 2 diabetesand heart failure, underscoring their potential as therapeutic agents for high-risk populations.Potential Benefits: SGLT2 inhibitors offer a spectrum of potential benefits, includingsubstantial reductions in AF risk, particularly in patients with type 2 diabetes and heart failure.These drugs have consistently demonstrated benefits in reducing heart failure hospitalizations,cardiovascular mortality, and stroke risk, which indirectly contribute to better AF management.Furthermore, SGLT2 inhibitors exhibit renoprotective properties by slowing theprogression of chronic kidney disease and reducing albuminuria, offering substantial benefitsfor AF patients with comorbid kidney disease. Metabolic improvements involving weight loss,blood pressure reduction, and favorable changes in lipid profiles contribute to enhanced cardiovascular health and reduced AF risk. Originally designed for diabetes management, thesemedications offer a holistic approach to AF risk reduction, particularly in patients with type 2diabetes and heart failure.

The field of human microbiome and gut microbial diversity research has witnessed a profound transformation, driven by advances in omics technologies. These advancements have unveiled essential connections between microbiome alterations and severe conditions, spurring the development of new frameworks through epidemiological studies. Traditionally, each individual was thought to harbor unique microbial communities acquired early in life, but recent research challenges this belief. The neonatal microbiome's onset, influenced by factors like delivery mode and maternal health, remains a subject of intense debate, hinting at potential intrauterine microbial processes. In-depth research reveals associations between microbiome profiles and specific health outcomes, ranging from obesity to neurodevelopmental disorders. Understanding these diverse microbiome profiles is essential for unraveling the intricate relationships between the microbiome and health outcomes.

Granulomatosis with polyangiitis (GPA), formerly known as Wegener’s granulomatosis, is a rare form of necrotizing granulomatous inflammation that predominantly affects medium and small size vessels. Generally respiratory tracts and kidneys are the most affected organs. Neurological manifestations of GPA usually involve the peripheral nervous system causing mononeuritis multiplex or and cranial nerve palsies. Central nervous system (CNS) involvement is rare and characterized by cerebral vasculitis, meningeal inflammation, or mass lesions. The CNS involvement is often linked to Ear Nose Throat (ENT) system disease. In this report, we present two cases of patients diagnosed with GPA who exhibit CNS involvement as first symptom. In the first one with an ischemic stroke while in the second with an atypical headache. In the first patient, a positive medical history indicating involvement of the Ear, Nose, and Throat (ENT) facilitated a precise diagnosis through the prompt execution of autoimmune screening. This, in turn, enabled a timely commencement of treatment, resulting in neurological improvement. In the second case, the significance of ENT involvement was initially overlooked in the context of pathological definition, leading to a substantial delay in diagnosis and an ultimately grim prognosis for the patient. The ENT involvement could be an easy marker to suspect GPA in patient with atypical CNS presentation and could help to make a prompt diagnosis.

(1) Background: The aim of this study was to analyze the relationship between the serum levels of soluble transferrin receptor (sTfR) and interleukin 4 (IL-4), and disease activity and organ mani-festations in SLE patients. (2) Methods: We studied 200 SLE patients and 50 controls. We analyzed disease activity, organ involvement, serum sTfR, IL-4, and interleukin-6 (IL-6) levels, and antinu-clear and antiphospholipid antibody profiles. (3) Results: The median serum levels of sTfR (p>0.000001) and IL-4 (p<0.00001) were higher in the study group than in the controls. SLE patients, compared to the controls, had significantly lower HGB levels (p<0.0001), a lower iron concentration (p=0.008), a lower value of total iron-binding capacity (TIBC) (p=0.03), and lower counts of RBC (p=0.004), HCT (p=0.0004), PLT (p=0.04), neutrophil (p=0.04), and lymphocyte (p<0.0001). Serum sTfR levels were negatively correlated with lymphocyte (p=0.0005), HGB (p=0.0001) and HCT (p=0.008), and positively correlated with IL-4 (p=0.01). Elevated serum sTfR >2.14 mg/dL was associated with an increased risk of myocardial infarction (OR: 10.6 95 CI 2.71–464.78; p=0.001), ischemic heart disease (OR: 3.25 95 CI 1.02–10.40; p=0.04), lung manifestations (OR: 4.48 95 CI 1.44–13.94; p=0.01), and hematological manifestations (OR: 2.07 95 CI 1.13–3.79; p=0.01), and with a reduced risk of neuropsychiatric manifestations (OR: 0.42 95 CI 0.22–0.80; p=0.008). Serum IL-4 was negatively correlated with CRP (p=0.003), and elevated serum IL-4 levels > 0.17 mg/l were associated with a reduced risk of mucocutaneous manifestations (OR: 0.48 95 CI 0.26–0.90; p=0.02). (4) Conclusions: In SLE patients, elevated serum levels of sTfR were associated with an increased risk of cardiovascular, pulmonary, and hematological manifestations, and with a decreased risk of neuropsychiatric manifestations. In contrast, elevated serum IL-4 levels were associated with a decreased risk of mucocutaneous manifestations.

The incidence of articular injury, particularly osteochondral fractures (OCF), has seen a notable increase in recent years. Regardless of their location, fragments might be overlooked by plain radiographs which might lead to osteoarthritis in the long run. Diagnostic imaging has a pivotal role in the assessment and classification of the fracture severity, as well as the presence of any associated dislocations. These fractures require surgical intervention for the restoration of joint function and the reduction of long-term complications. The paper aims to present the surgical correction and post-operative treatment of osteochondral fractures with absorbable implants in three children. Affected areas are discussed as follows: lateral condyle of the femur, patella, and radial head. Utilising absorbable implants for the management of OCFs provides numerous advantages, including the elimination of the need for reanaesthesia and reoperation, reducing complications, and enabling early rehabilitation. This approach also minimises the period of hospitalisation and proved effective in pediatric OCF treatment.

Background: Polycystic ovary syndrome (PCOS) is a common reproductive and endocrinological disease characterized by ovulatory dysfunction, polycystic ovaries, and hyperandrogenism. Adipokines are believed to contribute to developing PCOS and its accompanying metabolic complications such as dyslipidemia, insulin resistance, and cardiovascular diseases. Oncostatin M (OSM), a novel adipokine, plays a role in oogenesis, lipogenesis, and inflammation and may contribute to PCOS pathogenesis and its related metabolic problems. Methods: In this case-control study, the patients were grouped in a 1:1 ratio into either the PCOS (n = 32) or the control group (n = 32). Blood samples were obtained between the 3rd and 5th days of the menstrual cycle. Serum levels of fasting glucose, insulin, C-reactive protein (CRP), low-density lipoprotein, high-density lipoprotein, triglyceride, white blood cell count, thyroid-stimulating hormone, luteinizing hormone, follicle-stimulating hormone, total testosterone, prolactin estradiol, and OSM were analyzed. Results: OSM levels were significantly lower, but CRP levels were substantially higher in the PCOS group than in the control group (p = .002, p = .001, respectively). OSM was inversely correlated with total cholesterol, non-high-density lipoprotein cholesterol, fasting glucose, and the luteinizing hormone/follicle-stimulating hormone ratio (ρ = .329, p = .017; ρ = .386, p = .005; ρ = .440, p = .001; ρ = .316, p = .023, respectively). Conversely, there was no correlation between OSM and total testosterone level (ρ = .220; p = .118). In the context of inflammation and metabolic parameters, OSM was inversely correlated with CRP, Homeostatic Model Assessment for Insulin Resistance score (HOMA-IR), and low-density lipoprotein cholesterol (LDL) (ρ = .353, p = .019; ρ = .275, p = .048; ρ = .470, p &lt; .001, respectively). The performance of Oncostatin M for diagnosing PCOS showed 50% sensitivity, 75% specificity, and 63% accuracy (p = .009) in ROC curve analysis. Conclusions: Plasma OSM levels were considerably lower in patients with PCOS than in the control group, and this was inversely correlated with the hormonal and metabolic parameters of PCOS. Thus, OSM may be a novel therapeutic target for PCOS and metabolic complications.

S-adenosylmethionine (SAM) is considered to be a useful therapeutic agent for degenerative cartilage diseases, although its mechanism is not clear. We previously found that polyamines stimulate expression of differentiated phenotype of chondrocytes. We also found that cellular communication network factor 2 (CCN2) played a huge role in the proliferation and differentiation of chondrocytes. Therefore, we hypothesized that polyamines and CCN2 could be involved in the chondroprotective action of SAM. In this study, we initially found that exogenous SAM enhanced proteoglycan production but not cell proliferation in human chondrocyte-like cell line-2/8 (HCS-2/8) cells. Moreover, SAM enhanced gene expression of cartilage-specific matrix (aggrecan and type II collagen), Sry-Box transcription factor 9 (SOX9), CCN2 and chondroitin sulfate biosynthetic enzymes. Blockade of the methionine adenosyltransferase 2A (MAT2A) enzyme catalyzing intracellular SAM biosynthesis restrained the effect of SAM on chondrocytes. The polyamine level in chondrocytes was higher in SAM-treated culture than control culture. Additionally, alcian blue staining and RT-qPCR indicated that the effects of SAM on the production and gene expression of aggrecan were reduced by the inhibition of polyamine synthesis. These results suggest that the stimulation of polyamine synthesis and gene expression of chondrogenic differentiation factors, such as CCN2, account for the mechanism underlying the action of SAM on chondrocytes.

Psoriasis is a common chronic immune-mediated disease with many comorbidities and impacts on quality of life. Among the treatment options for psoriasis, phosphodiesterase-4 (PDE4) inhibi-tors are emerging with expanding options. PDE4 inhibitors play a pivotal role in the inflamma-tory cascade by degrading cyclic adenosine monophosphate (cAMP), contributing to pro-inflammatory mediator production. Apremilast, an oral PDE4 inhibitor, is an approved class for psoriasis. While effective, its adverse effects can limit its utility. Roflumilast, a topical PDE4 inhibitor, was recently also approved for psoriasis and shows promise in clinical trials. Crisaborole, approved for atopic dermatitis, has also been studied in psoriasis. This updated re-view summarizes evidence from randomized clinical trials regarding the efficacy and safety of PDE4 inhibitors in psoriasis treatment. By highlighting their potential benefits and limitations, this review provides valuable insights for clinicians and researchers aiming to optimize psoriasis therapy.

Colorectal cancer is a high-incidence tumor that has a high mortality rate due to its frequent metastasis to the liver. The difference in genes, proteins, and immune microenvironment between the primary and metastatic sites causes them to show different responses to treatment. Colorectal cancer liver metastasis patients also tend to show poorer treatment response and prognosis. Therefore, in this paper, we summarize the heterogeneity exhibited after colorectal cancer liver metastasis from five aspects (gene, transcriptome, protein, metabolism, and immunity), and we found that except for the genetic heterogeneity, the other four aspects exhibite significant heterogeneity, which might serve as a new therapeutic direction and a prognostic marker for patients with liver metastasis. Finally, the therapeutic modalities regarding tumors are rapidly evolving, and we have also summarize the new clinical therapeutic modalities currently proposed based on these heterogeneities, aiming to provide new therapeutic ideas for the clinical treatment of patients with colorectal cancer liver metastases.

Cancer is currently the second leading cause of death worldwide, second only to ischemic heart disease, with approximately 8.97 million estimated deaths. However, projections indicate that it is expected to surpass heart disease and become the leading cause of death by 2060. Lung, liver, and stomach cancer are the deadliest malignancies in the general population, while lung and breast cancer predominate as the primary causes of cancer-related death in men and women, respectively. Apart from conventional treatments, there is a growing interest in exploring plant-based drugs for cancer management. Elaeagnus angustifolia, a medicinal plant with a history of traditional use in various cultures for its therapeutic properties, has recently garnered attention as a potential cancer treatment due to its reported anti-cancer effects. This review article aims to comprehensively summarize the current research on Elaeagnus angustifolia and its therapeutic applications in cancer. It delves into in vitro studies investigating the plant's interactions with cancer cells, uncovering mechanisms such as apoptosis induction, cell cycle arrest, and modulation of signalling pathways. In addition to in vitro research, the review evaluates in vivo and preclinical studies assessing the safety and efficacy of Elaeagnus angustifolia in animal models, emphasizing the promising outcomes and underscoring the need for well-designed clinical trials to validate its potential benefits in human cancer patients. The review provides valuable insights into the current research on Elaeagnus angustifolia's role in cancer treatment. It underscores the necessity for further investigations, including clinical trials, to establish its safety, efficacy, and optimal use in cancer management.

Background: The aim of this study was to analyze the relationship between breastfeeding duration and adenoid size, snoring and acute otitis media (AOM). Methods: We analyzed the medical history, reported symptoms, ear, nose and throat (ENT) examination, and flexible nasopharyngoscopy examination of 145 children aged 3-5 years. Results: Breastfeeding duration of 3 and 6 months or more had a significant effect on the reduction of snoring (p = 0.021; p = 0.039). However, it had no effect on the adenoid size, mucus coverage and sleeping with an open mouth. Snoring was correlated with open mouth sleeping (p &lt; 0.001), adenoid size with a 75% A/C ratio or more (p &lt; 0.001), and adenoid mucus coverage in the Mucus of Adenoid Scale by Nasopharyngoscopy Assessment - MASNA scale (p = 0.009). Children who were breastfed for less than 3 months had more than a 4-fold greater risk of snoring. There was a statistically significant correlation between AOM and gender (p = 0.033), breastfeeding duration in groups fed 1, 3 or 6 months or more (p = 0.018; p = 0.004; p = 0.004) and those fed with mother’s breast milk 3 or 6 months or more (p = 0.009; p = 0.010). Moreover, a correlation was found between adenoid size and mucus coverage, tympanogram, and open-mouth sleeping (p &lt; 0.001). Independent factors of snoring in 3- to 5-year-old children were breastfeeding duration of less than 3 months (p = 0.032), adenoid size with an A/C ratio of 75% or more (p = 0.023) and open mouth sleeping (p = 0.001). Conclusion: Children breastfed for 3 and 6 months or more exhibited reduced rates of snoring. There was no effect of breastfeeding duration on adenoid size in children aged 3 to 5 years, suggesting that the link between breastfeeding duration and snoring is primarily associated with craniofacial development and muscle tone stimulation. A breastfeeding duration of 1 month or more plays a key role in reducing the rate of AOM. The mother’s milk plays a protective role against AOM. The presence of mucus might be responsible for snoring in preschool children. A medical history of breastfeeding should be taken into consideration when snoring children are suspected of adenoid hypertrophy.

Meningiomas are the most prevalent primary intracranial tumors. The majority are benign but can undergo dedifferentiation into advanced grades classified by World Health Organization (WHO) into Grades 1 to 3. Meningiomas tremendous variability in tumor behavior and slow growth rates complicate their diagnosis and treatment. A deeper comprehension of the molecular pathways and cellular microenvironment factors implicated in meningioma survival and pathology is needed. This review summarizes the known genetic and epigenetic aberrations involved in meningioma, with a focus on Neurofibromatosis type 2 (NF2) and non-NF2 mutations. Novel potential biomarkers for meningioma diagnosis and prognosis are also discussed, including epigenetic-, RNA-, metabolomics, and protein-based markers. Finally, the landscape of available meningioma-specific animal models is overviewed. Use of these animal models can enable planning of adjuvant treatment, potentially assisting in preoperative and postoperative decision-making. Discovery of novel biomarkers will allow, in combination with WHO grading, more precise meningioma grading, including meningioma identification, subtype determination, and prediction of metastasis, recurrence, and response to therapy. Moreover, these biomarkers may be exploited in the development of personalized targeted therapies that can distinguish between the 15 diverse meningioma subtypes.

Infectious diseases are one of the leading causes of death among children under the age of 5 with 60% of those deaths preventable with prophylaxis. Vaccinations prove to be the most succesfull and effective public health tool of infectious dieases preventions. Poland first implemented a program of mandatory childhood vaccinations in 1960. The program is updated each year and provides parents with a clear schedule to follow. The program includes vaccinations against 12 diseases (tuberculosis, hepatitis B, rotaviral disease, diphtheria, pertussis, tetanus, Haemophilus influenzae, Streptococcus pneumoniae, poliomyelitis, measles, mumps and rubella) mandatory for all children and funded by the government. It also includes recommended vaccinations which costs are covered by a patient. Immunization rates are monitored nationwide and reported to the Chief Sanitary Inspector. With recent outbreaks of infectious diseases among young children the obligation lies on the government to provide childhood immunizations, and largely on the physicians to provide reliable education about infectious diseases in children and safety of vaccinations to the parents.

Background and Aims: The impact of antibody response after direct-acting antiviral (DAA) therapy in hepatitis C virus (HCV)-infected recipients before and after liver transplantation (LT) is still undetermined. Methods: In this observational cohort study, we aimed to explore the association of changes in anti-HCV antibody titers after pre-LT DAA therapy with allograft injury, including biliary complications (BCs) and acute cellular rejection (ACR). Results: A total of 153 cases were enrolled from January 2015 to February 2021. Serum anti-HCV antibody titers were assessed before and after (day 30) LT. Among all recipients, 31/153 (20.3%) had pre-LT DAA therapy (DAA group) and 122/153 (79.7%) did not undergo pre-LT DAA therapy (DAA-naïve group). Higher incidence of post-LT BCs was observed in the DAA group (P = 0.028). Compared with the DAA-naïve group, the DAA group had a significantly higher mean level of anti-HCV titer upregulation (P = 0.0024); furthermore, among the recipients with BCs (n = 28) and ACR (n = 41), those in the DAA group exhibited significantly higher mean levels of anti-HCV antibody titer upregulation (P < 0.005). Conclusion: In conclusion, we speculated that anti-HCV antibody titer upregulation, which might have been induced by restoration of HCV-specific immune responses with pre-LT DAA therapy, were associated with post-LT allograft injury.

Background The coronavirus pandemic has led to the creation of clinical guidelines by a large number of professional medical communities. However, the quality and methodology of development of Russian clinical guidelines has been little studied. The continued relevance of studying the use of DOACs in patients with COVID-19 was the basis for conducting this study. Aim The objective of this study was to assess DOACs consumption and expenditures in Russian Federation during COVID-19 pandemic and to analyse domestic evidence base for the use of DOACs in COVID-19 patients through identifying all publicly available Russian-produced CPGs for the treatment of COVID-19 and assessing their quality as the source of recommendations for the use of oral anticoagulants for the prevention of thrombotic complications in COVID-19 patients. Methods We searched Russian databases for CPGs, published between 2020 and 2023. We identified 7 relevant documents that met our inclusion criteria. Three authors analyzed Russian clinical guidelines using a AGREE II questionnaire. We calculated DOACs DDD consumption according to Russian clinical guidelines and DDD consumption in patients with COVID-19 for the period 2020-2022. Results 7 clinical CPGs were analyzed with the AGREE II tool, it was revealed that experts gave the highest scores for the sections scope and purpose (from 62.98% to 100%), clarity of presentation (from 96.30% to 100%). The lowest scores were given for the sections stakenholder involment (33.33% to 64.81%), rigour of development (from 0% to 49.31%), applicability (from 23.61% to 50%), editory independence ( from 0% to 50%). When comparing the total score, it was found that two clinical guidelines received the highest scores - ROPNIZ (Livzan), ROPNIZ (Drapkina). The minimum score is registered with the NIIOZMM (Khripun) clinical guideline. No guideline received a total score of more than 70%. According to clinical recommendations, the consumption of apixaban and rivaroxaban is 15 DDD (30-day course of therapy), 22.5 DDD (45-day course of therapy). Consumption of apixaban in the Russian Federation in 2020 and 2021 corresponds to the indicators presented in clinical recommendations (in 2020 – 26.59 DDD per patient with COVID-19; in 2021 – 15.75 DDD per patient with COVID-19), and in 2022 – 10.67 DDD, which is below the recommended values. In 2020, consumption of rivaroxaban in the Russian Federation was 26.59 which corresponds to data from clinical recommendations; in 2021, consumption decreased to 7.87 DDD; in 2022 – 5.48 DDD, which is 2.74 times less than recommended.

Treatment of bladder cancer remains a critical unmet need and requires advanced approaches, particularly the development of local drug delivery systems. The physiology of the urinary bladder causes the main difficulties in the local treatment of bladder cancer: regular voiding prevents the maintenance of optimal concentration of the instilled drugs, while poor permeability of the urothelium limits the penetration of the drugs into the bladder wall. Therefore, much research effort is spent to overcome these hurdles, thereby improving the efficacy of available therapies. The explosive development of nanotechnology, polymer science and related fields has contributed to the emergence of a number of nanostructured vehicles (nano- and micro scale) applicable for intravesical drug delivery. Moreover, the engineering approach has facilitated the design of several macro-sized depot systems (centimeter scale) capable of remaining in the bladder for weeks and months. In this article, the main rationales and strategies for improved intravesical delivery are reviewed. Here, we focused on analysis of colloidal nano- and micro-sized drug carriers, and indwelling macro-scale devices which were evaluated for applicability in local therapy of bladder cancer in vivo.

The interplay between thrombosis and inflammation, known as thromboinflammation, is a significant pathway driving cardiovascular and autoimmune diseases, as well as COVID-19. Key modulators of this process have emerged as innate immune cells. Strategically positioned to promote thromboinflammation are neutrophils, the most predominant white blood cells in humans. Neutrophils can trigger an organized cell death pathway by releasing decondensed chromatin structures known as neutrophil extracellular traps. These structures are decorated with histones, cytoplasmic, and granular proteins, and have cytotoxic, immunogenic, and prothrombotic effects, which can accelerate disease progression. The activities of PAD4, which catalyses the citrullination of histones, and the neutrophil inflammasome are required for distinct steps leading to extracellular DNA release (NETosis). PAD4 activity has important implications for understanding the processes that drive thromboinflammation by linking the immunological function of neutrophils with the procoagulant and proinflammatory activities of monocytes and platelets. We will discuss how vascular blockages in thromboinflammation occur due to the interaction between neutrophil extracellular traps and ultra-large VWF (von Willebrand Factor). PAD4 activity has important implications for understanding the processes that drive thromboinflammation by linking the immunological function of neutrophils with the procoagulant and proinflammatory activities of monocytes and platelets. It will also review the mechanisms whereby vaso-occlusive events in thrombo-inflammation depend on the interaction of neutrophil extracellular traps with von Willebrand factor and suggest the importance of PAD4 in neutrophil inflammasome assembly and neutrophil extracellular traps in thrombo-inflammatory diseases such as atherosclerosis and CVD.

Glycosaminoglycans (GAGs) with unique structures from marine animals show intriguing pharmacological activities and negligible biological risks, providing more options for us to explore safer agents. Swim bladder is a tonic food and folk medicine, and its GAGs show good anticoag-ulant activity. In this study, two GAGs SJG-1.0 and GMG-1.0 have been extracted and isolated from the swim bladder of Sphyraena jello and Gadus morhua. The physicochemical properties, pre-cise structural characteristics, and anticoagulant activities of these GAGs were determined. The analysis results of the SJG-1.0 and GMG-1.0 showed that they were chondroitin sulfate (CS)/dermatan sulfate (DS) hybrid chains with molecular weights of 109.32 kDa and 123.13 kDa, respectively. They were mainly composed of the repeating disaccharide unit of -{IdoA-α1,3-GalNAc4S-β1,4-}- (DS-A). The DS-B disaccharide unit of -{IdoA2S-α1,3-GalNAc4S-β1,4-}- also existed in both SJG-1.0 and GMG-1.0. SJG-1.0 had a higher proportion of CS-O disaccharide unit -{-GlcA-β1,3-GalNAc-β1,4-}-, while GMG-1.0 contained higher proportion of CS-E disaccha-ride unit -{-GlcA-β1,3-GalNAc4S6S-β1,4-}-. The disaccharide compositions of the GAGs varied in a species-specific manner. Anticoagulant activity assay revealed that both SJG-1.0 and GMG-1.0 had potent anticoagulant activity, which can significantly prolong activated partial thrombosis time. GMG-1.0 also can prolong the thrombin time. SJG-1.0 showed no intrinsic tenase inhibition ac-tivity, while GMG-1.0 can obviously inhibit intrinsic tenase with EC50 of 58 nM. Their significantly different anticoagulant activities may be due to their different disaccharide structural units and proportions. These findings suggested that the swim bladder CS/DS hybrid chains with well-defined structure may be safer anticoagulants with low bleeding risk.

The TME, consisting of immune cells, fibroblasts, vessels, and the extracellular matrix, regulates tumor progression and therapy responses. TME-targeted therapies aim to transform this environment from supporting tumor growth to impeding it and fostering an effective immune response. This review examines the metabolic disparities between immune cells and cancer cells, their impact on immune function and therapeutic targeting, the TME components, and the complex interplay between cancer cells and non-tumoral cells. The success of TME-targeted therapies highlights their potential in achieving better cancer control or even a cure.

The skeletal muscle plays a critical role in regulating systemic blood glucose homeostasis. Impaired skeletal muscle glucose homeostasis associated with type 2 diabetes mellitus (T2DM) has been observed to significantly affect the whole-body glucose homeostasis, thereby resulting in other diabetic complications. T2DM does not only affect skeletal muscle glucose homeostasis, but it also affects skeletal muscle structure and functional capacity. Given that T2DM is a global health burden, there is an urgent need to develop therapeutic medical therapies that will aid in the management of T2DM. Prediabetes is a prominent risk factor of T2DM that usually goes unnoticed in many individuals as it is an asymptomatic condition. Hence, research on prediabetes is essential because establishing diabetic biomarkers during the prediabetic state would aid in preventing the development of T2DM, as prediabetes is a reversible condition if it is detected in the early stages. Literature predominantly documents the changes in skeletal muscle during T2DM, but the changes in skeletal muscle during prediabetes remain unknown. In this review, we seek to review the existing literature on prediabetic and T2DM associated changes in skeletal muscle function.

The relationship between arterial stiffness and oxygen uptake (VO2) in patients with acute myocardial infarction (AMI) remains unclear. We aimed to investigate this relationship and factors contributing to VO2 in patients with AMI. The role of arterial stiffness in cardiac-skeletal muscle coupling during exercise was then elucidated. The exercise capacity via cardiopulmonary exercise testing (CPX), cardio-ankle vascular index (CAVI), and body composition of 101 patients with AMI were measured at discharge. Patients were categorized based on their CAVI into three groups: (i) normal (CAVI: ≤7.9), (ii) borderline (CAVI: 8.0–8.9), and (iii) abnormal (CAVI: ≥9.0). Subsequently, VO2 was compared among these groups. The relationship between the CAVI and peak VO2 (VO2 Peak) during CPX and factors contributing to VO2 Peak were investigated. The abnormal CAVI group had a significantly lower VO2 Peak than the normal and borderline groups. The CAVI was associated with VO2 Peak in patients with AMI. Furthermore, the CAVI was found to be a factor contributing to VO2 Peak. These findings suggest that arterial stiffness in tissue blood distribution and blood supply defines systemic exercise limits in patients with AMI. This suggested that arterial stiffness plays a significant role in cardio-vascular-skeletal muscle coupling.

Dermatophagoides pteronyssinus (Der p) subcutaneous immunotherapy (SCIT) has demonstrated efficacy in clinical trials of childhood allergic rhinitis (AR). Currently, there is a lack of some generally accepted biomarkers that may predict the clinical response to SCIT to eventually achieve personalized therapy. In this study, 28 children with AR received Der p SCIT for 26-30 months at baseline, and four efficacy endpoints, serum interleukin (IL)-5, periostin, Der p-specific IgE (sIgE), and Der p sIgG4, were measured by ELSIA. Clinical symptoms and characteristics were assessed by questionnaires, and the associations among periostin, Der p 2 sIgE and clinical efficacy were analyzed. The results showed that SCIT demonstrated a significant reduction in Der p 1 sIgE (P < 0.05) and Der p 2 sIgE (P < 0.01), an increase in Der p sIgG4 (P < 0.001) and an improvement in clinical efficacy at the fourth efficacy endpoint compared with that at baseline. A positive linear correlation was found in serum periostin and Der p sIgE (Pearson correlation=0.8868, P=0.045), Der p sIgG4 (Pearson correlation=-0.9025, P=0.036), and clinical efficacy. Importantly, the concentration of serum Der p 2 sIgE showed a positive linear correlation with clinical efficacy and serum periostin (Pearson correlation=0.9581, P=0.010). These results suggest that SCIT can result in reduced type 2 cytokines and Der p sIgE and has long-term efficacy in children with AR. Der p 2 sIgE has a positive linear correlation with clinical efficiency and serum periostin and may be a useful biomarker for the prediction of SCIT.

CD44 is a type I transmembrane glycoprotein, and possesses various isoforms which are largely classified into CD44 standard and CD44 variant (CD44v) isoforms. Some variant-encoded regions play critical roles in tumor progression. However, the function of CD44 variant 4 (CD44v4)-encoded region has not been fully understood. Using peptide immunization, we developed an anti-CD44v4 mAb, C₄₄Mab-108, which is useful for flow cytometry, western blotting, and immunohistochemistry. In this study, we determined the critical epitope of C₄₄Mab-108 by enzyme-linked immunosorbent assay (ELISA). We used the alanine (or glycine)-substituted peptides of the CD44v4-encoded region (amino acids 271-290 of human CD44v3-10), and found that C₄₄Mab-108 did not recognize the alanine-substituted peptides of D280A and W281A. Furthermore, these peptides could not inhibit the recognition of C₄₄Mab-108 in flow cytometry and immunohistochemistry. The results indicate that the critical binding epitope of C₄₄Mab-108 includes Asp280 and Trp281 of CD44v3-10.

(1) Background: Thrombophilia is a tendency towards hypercoagulability, and it is increased by pregnancy, and peaking around delivery.; (2) Methods: 80 Eighty thrombophilia patients admitted for delivery between 1/10/2017 and 1/12/2021 were prospectively studied, together with 80 eighty age- and para-matched control patients. Patients were admitted for delivery at term by means of cesarean section. The inflammation indexes from the complete blood count values analysis, in during both the 24 hours before and the 24 hours after labor—, extracted from the hospital’s medical records—, were calculated, and then correlated with uterine involution.; (3) Results: In pregnant patients treated for thrombophilia patients, the patients who did not manage to have close their uterine cavity closed with in the first 24-48 hours had significantly higher SII and AISI inflammation indexes SII and AISI , than the onesthose who did manage to have their uterine cavity closed their uterine cavity. In pregnant patients treated for thrombophilia patients, MLR is higher in patients without the Rh factor than in those with the Rh factor. In non-thrombophilia patients, PLR was significantly higher as compared to treated thrombophilia patients. In non-thrombophilia patients, MCVL increased with age and, before labor, while SII and AISI increased with age, postpartum. ; (4) Conclusions: There may be an underlying inflammation state that persisted despite treatment in some pregnant thrombophilia pregnant patients.

(1) Background: Ulcerative colitis (UC) is characterized by immune system dysregulation with frequent extraintestinal manifestations, including airways involvement. Reduction in CO diffusing capacity and functional alterations in small airways have been described. The extended analysis of Fractional Exhaled Nitric Oxide (FeNO), may distinguish the sites of production and the presence of small airways inflammation being a useful, non-invasive marker for these patient’s follow up. The aim of our study was to compare PFTs, FeNO and CANO values of UC patients with different clinical disease activity and healthy subjects to reveal lung function abnormalities and the presence of subclinical airway inflammation. (2) Methods: We enrolled 42 adult outpatients with different clinical activity stages of UC (mean age 39±13 years) and a healthy control group of 41 subjects (mean age 29±3 years). C-reactive protein (CRP) and FeNO values at different flows (50,100 and 200 ml/sec) were collected. All patients performed pulmonary function tests (PFT’s) with static volumes and diffusing capacity (DLCO). (3) Results: FENO, CANO and CRP values were significantly increased in UC patients when compared with controls (p=0.02 and p&lt;0.0001, respectively) and proportionally to the disease activity (FeNO class 3: 27.1 ppb vs class 1-2: 6.2 ppb; CANO values class 3: 8.1 ppb vs class 1-2: 2.0 ppb (p &lt; 0.0001). TLC and DLCO were significantly reduced in UC patients compared to controls (p=0.011 and p&lt;0.0001, respectively). (4) The results of this study show significant lung functional abnormalities in UC patients and suggest the presence of airway inflammation directly correlated with the disease activity suggesting an integrated approach in routine assessment.

Phantom Limb Pain (PLP) is a challenging condition affecting a significant proportion of amputees. In this article we describe the case of a 54-year-old Paralympic athlete with Phantom Limb Syndrome following right leg amputation and widespread sports-related enthesitic pain, who underwent a Whole Body Cryostimulation (WBC) cycle, an emerging treatment known for its rapid pain-relieving and anti-inflammatory effects. Assessments were conducted before and after a 10-session WBC cycle, including pain and quality of life assessment, and use of medications. A substantial reduction in enthesitic pain, PLP intensity, paresthesia, tingling related to atmospheric events and an improved function and quality of life were reported after the WBC cycle and lasted for two weeks. One month after WBC, the enthesitic pain following sports activity and PLP gradually returned but with lesser intensity. Similarly, the stump's sensitivity to atmospheric changes returned but with lower frequency. Pain at night remained lower than before WBC with significantly improved quality of sleep. This case study suggests that WBC could be a valuable adjuvant treatment for alleviating PLP. Controlled studies are warranted to validate the findings of this case-report and elucidate the mechanisms underlying the positive effects of WBC in this condition.

Whole blood viscosity, a hemorheological factor, is currently used for diagnosis, as it is correlated with various vascular diseases that are difficult to diagnose early with a general blood test. It was determined that it was necessary to set reference intervals for further studies and utilization of whole blood viscosity in cats, a representative companion animal, and this study was conducted. 50 healthy cats were recruited for the study and whole blood viscosity, complete blood count, and serum chemistry tests were performed. The reference intervals of whole blood viscosity were 15.169 to 43.684 cP at a shear rate of 1 s-1 reflecting diastole, and 3.524 to 5.544 cP at a shear rate of 300 s-1 reflecting systole. Red blood cells, hematocrit, hemoglobin, white blood cells, and neutrophils in the complete blood count, and total protein, albumin, globulin, and cholesterol in the serum chemistry were significantly correlated with whole blood viscosity. The results of this study set reference intervals of whole blood viscosity for healthy cats in a wide shear rate range that has not yet been fully established and investigated its correlation with other blood indicators.

A partial or complete pulpotomy is a type of vital pulp therapy (VPT) that aims to remove the in-flamed, infected pulp, leaving behind healthy, vital pulp that is capable of healing. VPT has gained renewed popularity as a treatment option in permanent mature posterior teeth with irre-versible/moderate-severe pulpitis, its high success rates matching that of root canal treatment (RCT). There is currently no consensus regarding diagnostic and prognostic predictors of success of pulpotomies for managing such cases. Therefore, we conducted a scoping review to identify and analyze how these factors affect the outcome of treatment. A literature search using the PRISMA guidelines was undertaken using PubMed and Scopus on July 7, 2023. A total of 22 studies met the inclusion criteria and were qualitatively analyzed by two reviewers. The follow-ing diagnostic and prognostic factors were recognized and discussed; presenting signs and symptoms, periapical diagnosis, bleeding time, indicators of inflammation (bleeding time, con-centration of inflammatory biomarkers), patient age and medical status, the depth, activity and location of caries, and restorative factors. Based on the studies assessed, there is limited evidence to support their prognostic value. Further research is necessary to identify solid predictors of outcome.

The quest for surgical advancements regarding the enhancement of the submental and cervicofacial regions has witnessed a remarkable upsurge in recent years. Informed patients are actively seeking sophisticated plastic surgery techniques to achieve comprehensive rejuvenation in these specific areas. Our clinical practice encounters an annual influx of approximately 400 patients, with 20% of them aged over 60, seeking facial rejuvenation encompassing the details of lower third of the face and neck. Common concerns expressed by these patients include sagging of the jawline, the emergence of deep perioral wrinkles, and the formation of "marionette lines" within the lower third of the face. Furthermore, the manifestation of age-related signs, including neck laxity, submental adipose accumulation, "witch's chin" deformity, and weakened platysma musculature, is frequently encountered within this intricate anatomical domain. This review aims to summarize the recent technical improvements, historical evolution, indications, postoperative care and challenges for facial rejuvenation of the lower third of the face and neck. Lastly, the application of minimally invasive procedures as part of a comprehensive approach to an aging face will also be discussed.

Understanding tumor attachments and management of feeding arteries are very important factors to achieve safe resection of skull base meningioma. We examined the distributions and frequencies of feeding arteries in skull base meningioma by cerebral angiography, and also assessed relationships to tumor attachment for skull base meningioma. We enrolled patients with skull base meningioma who underwent MRI and cerebral digital subtraction angiography (DSA), from September 2015 to October 2022. Subjects comprised 115 patients (32 males, 83 females; mean age, 52.7 years) with 117 meningiomas showing tumor attachments around the “cavernous sinus to upper part of the clivus” (Area 1), “lower part of the clivus to foramen magnum” (Area 2), and “tentorium around the petrous bone” (Area 3). We examined feeding arteries based on cerebral angiography and counted the number of related feeding arteries. Particularly frequent arteries, such as the dorsal meningeal artery (DMA), ascending pharyngeal artery (APA), tentorial artery (TA), and petrosal branch (PB) of the middle meningeal artery (MMA) were analyzed for associations of tumor attachment to Areas 1–3. DMA, APA, TA, and PB are very frequent feeding arteries among skull base meningiomas. In some cases, the artery of the foramen rotundum, posterior ethmoidal artery, recurrent meningeal artery, posterior meningeal artery, etc., supply blood to the skull base meningioma. Meningiomas with DMA as a feeding artery correlated strongly with tumor attachment to Area 1 (p&lt;0.001). Meningiomas with APA correlated strongly with tumor attachment to Area 2 (p&lt;0.001). Meningiomas with TA correlated strongly with tumor attachment to Area 3 (p&lt;0.001). PB correlated with Area 3 (p&lt;0.05). Visualization of these arteries suggests tumor attachments to the correlated areas. An accurate anatomical understanding of tumor attachment and feeding arteries is essential to determine appropriate surgical strategies for skull base meningioma. Pre-operative DSA can provide further understanding of the feeding arteries and attachments of skull base meningioma.

Introduction: Crohn's disease (CD) is a chronic inflammatory granulomatous disease that can affect the entire gastrointestinal tract. It is characterized by various extraintestinal manifestations (EIM), of which oral manifestations (OM) are often possible. One of the possible OM is periodontal disease (PD) a chronic inflammatory condition of the supporting tissues of the teeth. This study aimed to show the existence of a mutual relationship between the clinical activity of PD and the clinical and endoscopic activity of CD. Materials and methods: Using one clinical and two endoscopic indexes for the assessment of CD activity and clinical attachment loss (CAL), bleeding on probing (BOP), pocket probing depth (PPD) and radiographic bone loss (RDL) on dental panoramic tomogram to assess PD in CD patients. Results: A total of 38 patients underwent the entire study process, of which 20 patients with CD and 18 patients with CD and PD. Considering all CD activity scores, there were 26 patients with active disease, and half of them had PD, and 85.7% of operated patients had active CD. Values of CAL, PPD, BOP and RBL were higher in active CD than remission, except BOP when compared to CDAI score which was higher in remission of CD. Discussion and conclusion: The results of this study indicate that there is a connection between the activity of CD and the worse condition of the supporting tissues of the gums in the oral cavity which is important to keep in mind the necessity of referring patients with CD to a dentist for timely and adequate therapeutic measures.

This comprehensive scientific review provides an in-depth analysis of both the natural compounds, pyrethrins, and their synthetic derivatives, pyrethroids, focusing on their classification, biosynthesis, mechanism of action, general and pharmaceutical uses, as well as their toxicity and environmental impact. Pyrethrins, derived from certain plant species, have long been recognized for their potent insecticidal properties. The review begins by examining the classification of pyrethrins and pyrethroids, elucidating their structural characteristics and unique features within the field of natural and synthetic compounds. The biosynthetic pathways responsible for producing pyrethrins in plants are discussed, highlighting the enzymatic reactions and genetic regulation involved. In addition, the synthesis of pyrethroid derivatives is explored, including both natural and synthetic sources and potential optimization strategies. Understanding the mechanisms of action by which pyrethrins and pyrethroids exert their insecticidal effects is a crucial aspect of this review. Complex interactions with the nervous systems of target organisms are examined, providing insights into their selective toxicity and modes of action. In addition, the various applications of these compounds are explored, from their use in agriculture for pest control to their incorporation into household insecticides and potential pharmaceutical applications. The review also critically evaluates the potential toxicity of pyrethrins and pyrethroids to human health. By consolidating current knowledge and research findings, this review provides a comprehensive understanding of the properties and applications of pyrethrins and pyrethroids, highlighting their benefits and risks, and the importance of responsible and sustainable use in various areas.

The decompensation trajectory check is a basic step to assess the clinical course and to plan future therapy in hospitalized patients with acute heart failure (ADHF). Due to the atypical presentation and clinical complexity, trajectory checks can be challenging in the oldest old patients with acute HF. Point of care ultrasound (POCUS) proved to be helpful in the clinical decision-making of patients with dyspnea, but no study has attempted to verify its effectiveness in predicting determinants of HF in-hospital worsening. In this single-center prospective study, we consecutively enrolled patients aged 75 or older hospitalized with acutely decompensated HF in a tertiary care hospital. All the patients underwent complete clinical examination, blood tests, and POCUS including Lung Ultrasound, Focused Cardiac Ultrasound, Pleural Effusion score (PEFs), and Inferior Vena Cava (IVC) assessment. Out of 184 patients hospitalized with ADHF enrolled in the study, sixty experienced HF in-hospital worsening. No differences were found among patients with HF worsening and controls in terms of age, gender, frailty, and left ventricular ejection fraction. By multivariable logistic analysis, total PEFs [aOR: 1.15 (CI95% 1.02– 1.33), p = 0.043], and IVC collapsibility [aOR: 0.90 (CI95% 0.83 – 0.95), p = 0.039] emerged as independent predictors of acute HF worsening after extensive adjustment for potential confounders.

Febrile neutropenia (FN) is a major concern in patients undergoing chemotherapy for diffuse large B-cell lymphoma (DLBCL); however, the overall risk of FN is difficult to assess. This study aimed to develop a model for predicting the occurrence of FN in patients with DLBCL. In this multicenter, retrospective, observational analysis, a multivariate logistic regression model was used to analyze the association between FN incidence and pretreatment clinical factors. We included adult inpatients and outpatients (aged ≥ 18 years) diagnosed with DLBCL who were treated with chemotherapy. The study examined 246 patients. Considering FN occurring during the first cycle of chemotherapy as the primary outcome, a predictive model with a total score of 5 points was constructed as follows: 1 point each for viral hepatitis, extranodal involvement, and a high level of soluble interleukin-2 receptor and 2 points for lymphopenia. The area under the receiver operating characteristic curve of this model was 0.844 (95% confidence interval: 0.777–0.911). Our predictive model can assess the risk of FN before patients with DLBCL start chemotherapy, leading to better outcomes.

Lung cancer remains the leading cause of cancer-related mortality worldwide. The main issue is the absence of a screening test available in clinical practice; the identification of non-invasive biomarkers is thus an urgent clinical necessity. Currently, low-dose computed tomography (LD-CT) demonstrates a 20% reduction of lung cancer mortality. However, it is not particularly suitable for clinical practice because of the costs, radiation, and the false positive rate. Several studies have therefore focused on research into biomarkers in body fluids. Despite the power of certain molecules to distinguish lung cancer patients from healthy subjects, no biomarker has yet been shown to significantly and reliably influence clinical decisions or to be translated from the laboratory to clinical practice. We performed an overview of the peer-reviewed biomedical literature published in the last 10 years on the research regarding biomarkers for the early diagnosis of lung cancer via a comprehensive analysis of the reviews published this past year. Our main aim was to bring to light the limitations and strengths of the research already conducted. Furthermore, future prospectives have been explored, bearing in mind the management of clinical trials and their integration into clinical practice.

This article discusses the fabrication of pullulan/polyvinyl alcohol (PVA) and PVA blends as carrier polymers for drug delivery. This study utilized coaxial electrospinning to encapsulate doxorubicin (DOX), a common anticancer drug, within nanofibers, which helped mitigate the adverse effects of DOX on normal cells. The study also demonstrated that the coaxial electrospinning technique using PVA/pullulan cores was effective in inhibiting the attachment and proliferation of HeLa cells, a type of cervical cancer cell. The use of pullulan/PVA and PVA blends as carrier polymers in conjunction with coaxial electrospinning could provide a safe and effective drug delivery system for the treatment of cervical and other solid malignancies. The study concluded that nanofibers showed promising results in inhibiting the growth of HeLa cells, indicating their potential as safe and effective drug delivery systems for treating cervical cancer and other solid malignant tumors.

Background The Delta Neutrophil Index (DNI), a prodiagnostic marker for sepsis, utilizes leukocyte count. Platelet activation, similar to leukocytes, plays a crucial role in host defence against pathogens and may serve as a predictor of sepsis outcome. However, the combined evaluation of Mean Platelet Component (MPC) and DNI in assessing sepsis has been rarely used. Methods To assess the prodiagnostic validity of simultaneous utilization of DNI and MPC in cases of human febrile sepsis, we conducted measurements of cellular indices, including DNI and MPC, as well as molecular biomarkers such as procalcitonin (PCT) and C-reactive protein (CRP). This study was carried out on patients admitted to the emergency department with suspected sepsis. Results Using a cutoff value of 2.65%, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of DNI in sepsis were found to be 69%, 73.9%, 77.9%, and 64.1%, respectively. Furthermore, significant differences in DNI and MPC levels were observed between the sepsis and non-sepsis groups (6.7±7.8% versus 2.1±2.2%, P=0.000 and 26.0±1.9 g/dl versus 26.8±1.4 g/dl, P=0.002), respectively. Notably, there was a negative correlation between DNI and MPC, with the strength of the correlation varying based on the cause of sepsis. By setting the cutoff value for DNI at 6.2%, the sensitivity, specificity, and NPV improved to 100%, 80.3%, and 100%, respectively, although the PPV remained at 10.6%. Importantly, the DNI≥6.2 group exhibited a higher incidence of death (10.9%, 5/46) and multiorgan failure (19.6%, 9/46) compared to the DNI<6.2 group (0.0%, 0/46 and 0.0%, 0/167, respectively) (P=0.000 and P=0.000, respectively). Conclusions In our study, DNI demonstrates superior effectiveness compared to other molecular biomarkers such as CRP and procalcitonin in distinguishing febrile septic patients from febrile nonseptic patients and predicting prognosis. Additionally, there exists a negative correlation between MPC and DNI, making MPC a valuable marker for differentiating the etiology of sepsis. These findings hold significant clinical implications as DNI/MPC is a cost-effective and readily applicable approach in various impending sepsis scenarios. Notably, this study represents the first examination of the prodiagnostic validity of simultaneously employing DNI and MPC in human cases of febrile sepsis.

Leukodystrophies, also known as demyelinating diseases, mainly affect the CNS. Clinical presentation of different types of leukodystrophies can be nonspecific and thus, imaging techniques like MRI can be used for a more definitive diagnosis. These diseases are characterized as cerebral lesions with characteristic demyelinating patterns, which can be used as differentiating tools. In this review, we talk about these MRI imaging findings for each leukodystrophy, associated genetics, blood work that can help differentiate, emerging diagnostics, and follow up imaging strategy. The leukodystrophies discussed in this paper include X-linked adrenoleukodystrophy, Metachromatic leukodystrophy, Krabbe’s disease, Pelizaeus-Merzbacher disease, Alexander’s disease, Canavan disease, and Aicardi-Goutières Syndrome.

Serologic measures of tissue transglutaminase (tTG) immunoglobulin A (IgA) and deamidated gliadin peptide (DGP) IgA and immunoglobulin G (IgG) are hallmark tests utilized when diagnosing individuals for celiac disease (CeD) and for monitoring adherence to a gluten-free diet (GFD), currently the only available treatment for CeD. We address two issues in this study: (i) the relapse to seropositivity for CeD patients who resume a gluten containing diet and (ii) the correlation between two different tTG-IgA assays near the upper limit of normal (ULN) designated thresholds. Regarding the first issue, often a suspected CeD individual is put back on a gluten diet to return to their serologic levels. However, we show it requires a substantial amount of gluten for serology to return to a positive level. For example, in one study of 22 patients treated with placebo and taking 84 g of gluten over 6 weeks, only 2 converted from seronegative to seroposi-tive for tTG-IgA. Regarding the second topic, we compare the relationship for different serologic assays, namely tTG-IgA AB (recombinant, ULN=4 Units/mL) vs. tTG-IgA (non-recombinant, ULN=20 Units). There is a strong correlation by both measurements as evidenced by a Pearson coefficient of R = 0.8584. However, we observed that the cross-correlation in terms of sensitivity and specificity improved substantially by using an ULN value of 3 instead of 4 for the tTG-IgA AB (recombinant) assay. This result suggests that assay thresholds used for initial diagnosis in patients who have not yet started a GFD may need to be adjusted for monitoring and in the setting of a diagnostic gluten challenge.

Objective: To evaluate which risk factors contribute directly or indirectly to Toxoplasma gondii infection in patients with ocular toxoplasmosis. Methods: Between 2018-2020, a total of 306 patients were selected, and treated at the Retinology Outpatient Clinic of the Specialty Hospital of Sāo José do Rio Preto, in the state of São Paulo. After the fundoscopy test, the Enzyme Linked Fluorescent Assay (ELFA) was used to determine IgG and IgM class anti-Toxoplasma gondii antibodies. Results: The results showed that individuals aged 60 years or older, and women who had a previous pregnancy, (p=0.000, OR= 8.137 and 95 % CI = 2.562 – 25.844), (p=0.016, OR= 7.395 and CI 95 % = 1,449 – 37,725) respectively, were 48.6 % more likely to develop ocular toxoplasmosis. Conclusion: In this way, previous pregnancy is a risk factor for the reactivation of toxoplasma, as well as for the generation of retinochoroiditis in previously infected women.

Collision tumors, even uncommon, characterized by two distinctive (morphological, as well immunohistochemical) and spatially independent tumor components in the same location, are always puzzling for clinicians, pathologists and patients because they don’t fit in usual approaching schemes, neither diagnostic, nor therapeutic. Reviewing the specialized literature, until now, collision tumors have been reported in multiple locations such as the skin, esophagus, stomach, liver, kidney, bladder, adrenal gland or thyroid. We report a case of coexistence on the same site of a malignant tumor of ascending colon and a benign one emerging from peritoneal lining, thought initially by the surgeon to be right sided serosal carcinomatosis. But the histopatological examination reveals that those multiple serosal nodules were benign granular cell tumors collided with highly aggressive transparietal signet-ring colon carcinoma. These results put the patient's prognosis and therapeutic strategy in a different light than the clinical-imaging and intraoperative assessment.

Although multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) that results in many neurological disabilities, optic neuritis (ON) is developed in some MS patients. However, the molecular mechanism of ON remains unknown. Galectins, β-galactoside-binding lectins, are involved in various pathophysiology. We have previously shown that galectin-3 (gal-3) is associated with the pathogenesis of experimental autoimmune encephalomyelitis (EAE), its animal model for human MS. In the current study, the expression of gal-3 was explored in the visual pathway of the EAE mice to clarify the pathogenesis of ON. Immunohistochemical analysis demonstrated that expression of gal-3 was increased in the visual pathway of the EAE mice during the peak disease, compared with naïve and EAE mice during the chronic disease. Expression of gal-3 was observed in mainly microglia/macrophages and astrocytes in the visual pathway of the EAE mice. In addition, gal-3+Iba-1+ cells with the phagocytic activities reflected by immunostaining with cathepsin-D were accumulated at demyelinating lesions in the visual pathway during peak disease of EAE. Moreover, NLRP3 expression was also detected in most gal-3+Iba-1+ cells. These results indicate a considerable possibility that gal-3 regulates the NLRP3 signaling in microglia/macrophages, followed by neuroinflammatory demyelination in ON. By contrast, astrocytic expression of gal-3 was also observed from the peak to the chronic disease. Taken together, the current study suggests a critical role of gal-3 in the pathogenesis of ON and proposes gal-3 in glial cells as a potential therapeutic target for ON.

Introduction: The coronary flow reserve (CFR) is a sign of early-stage coronary artery disease (CAD). Plasma atherogenic index (PAI) is related to atherosclerosis and cardiovascular mortality. Therefore, our aim was to determine CFR and PAI in patients with primary hyperparathyroidism (PHPT) and investigate whether PAI can be used in the detection of early-stage CAD. Material and Methods: The sample was comprised of 44 patients with PTHT and 33 healthy volunteers. We defined CFR as the ratio of the hyperemic diastolic peak velocity to the baseline diastolic peak velocity. PAI values were calculated with the formula of log 10 triglyceride (TRG) / high-density lipoprotein (HDL). Result: The comparison of the groups for PAI and CFR demonstrated that PAI levels were significantly higher while CFR levels were significantly lower in the PTHT patients (p<0.01, p=0.01, respectively). The correlation analysis revealed that CFR was negatively correlated with PAI and TRG (PAI- p<0.0001 r=-0.537).The multivariate logistic regression analysis showed that only a high PAI level (OR: 151.6, 95% confidence interval (CI): 4.1-5480, p=0.006) was an independent predictor of reduction in CFR in PHPT patients. Conclusion: Overall, we found an independent correlation between PAI and CFR values. Hence, PAI may be useful in identifying PHPT patients facing a high risk of adverse cardiovascular events and may also allow early diagnosis of subclinical atherosclerosis.

Irrigation is crucial in cleaning and disinfection of the root canal system, because endodontic instruments are unable to reach a large part of the root canal system (isthmuses, accessory canals, apical ramifications) and bacteria that can reside. Sodium hypochlorite (NaOCl) is currently used as irrigant in root canal therapies for its non-specific protheolytic and antimicrobial properties, but undesirable effects may be observed especially when used near the terminus of apical foramen. This study aims to evaluate antimicrobial properties of Thyme Essential Oil (TEO) used alone or in combination with NaOCl against different bacterial strains, especially Staphylococcus aureus and Streptococcus mutans. TEO non-cytotoxic concentration (9,28mg/mL) showed antimicrobial properties comparable to NaOCl after 1min of contact, both in presence of organic material (6% sheep blood). Moreover, the combination of TEO and NaOCl did not compromise their individual antimicrobial properties at the same time of contact. These data suggest that TEO could be used as antimicrobial irrigant in root canal therapies in association with NaOCl, to reduce concentration of NaOCl and its undesirable side effects. Due to the absence of cytotoxic effects at tested dilution, TEO could be safely used also near the terminus of apical foramen for its cytocompatibility.

Cytokine adsorption can resolve different complications characteristic of transplantation medicine, such cytokine storm activation, blood immuno- and AB0- incompatibilities but can also be performed for the treatment of various life-threatening conditions, such as sepsis, acute respiratory distress syndrome (ARDS), and cardiogenic shock, all of which can contribute to adverse clinical outcomes during transplantation. After surgery, dysmetabolism and stress response limit successful graft survival and can lead to primary (PGD) or secondary graft dysfunction. In this clinical context, and given that a major problem in transplant medicine is that the demand for organs far exceeds the supply, a technological innovation such as a hemoadsoption system could greatly contribute to increasing the number of usable organ donors. The objectives of this review are to describe the specific advantages and disadvantages of the application of cytokine adsorption in the context of transplantation and also to examine, before and/or after organ transplantation, the benefits of addition of a complementary cytokine adsorption therapy protocol.

Mucormycosis is an opportunistic fungal infection that is increasingly affecting patients with Coronavirus Disease (COVID-19). This connection is particularly pronounced in specific populations, including individuals with diabetes or those who have recently undergone corticosteroid therapy. Additionally, Cytomegalovirus (CMV) infection is a frequent complication among COVID-19 patients who have previously received corticosteroid or other immune-modulatory treatments. In this case report, we present the clinical details of a 56-year-old male who developed post-COVID pneumonia complicated by both cutaneous mucormycosis and CMV infection.

Blood biomarkers represent a promising future for studying cognitive impairment, particularly in Alzheimer's Disease (AD), as they offer a non-invasive alternative to cerebrospinal fluid tests and have potential as population screening tools. However, the relationships between these biomarkers and specific cognitive functions, as well as their utility in predicting longitudinal cognitive decline, are not yet fully understood. This descriptive review surveys the literature from 2018 to 2023, focusing on the associations between Amyloid-β, Total Tau, Phosphorylated Tau (p-tau), Neurofilament Light (Nfl), and Glial Fibrillary Acidic Protein (GFAP) with cognition. The reviewed studies are heterogeneous, varying in design and population (mixed, cognitively impaired, or unimpaired), and show results that are sometimes conflicting. Generally, cognition positively correlates with Aβ levels, especially when evaluated through the Aβ42/Aβ40 ratio. In contrast, Tau, Nfl, and GFAP levels typically show a negative correlation with cognitive performance. While p-tau measures tend to show stronger associations with cognitive functions than other biomarkers, no single blood marker has emerged as predominantly associated with a specific cognitive domain. These findings add to our understanding of the complex relationship between blood biomarkers and cognitive performance and underscore their potential utility in clinical evaluations of cognition.

Introduction: This analysis is conducted as a part of a quality improvement project aiming at identifying racial disparity in inpatient stroke quality of care. Methods: Get With The Guidelines (GWTG) database was used to identify all patients discharged with any stroke diagnosis between January and December 2021. Additional chart review was conducted to ensure the accuracy of racial/ethnic categorization. The sample was dichotomized to White vs non-White groups and compared with univariate analysis. Results: The study sample comprised 1,408 encounters (1,347 patients). Mean age 71±15 years, 51% women, 82% White patients, 15% non-White patients, 72% acute ischemic stroke (AIS); 15% transient ischemic attack (TIA), 9% intracerebral hemorrhage (ICH), 3% subarachnoid hemorrhage (SAH), and 1% stroke not otherwise specified. Non-White patients were younger, had fewer concomitant diagnoses, lower proportion of TIA and higher proportion of ICH (p=0.004). In AIS cohort, compared to White patients, non-White patients had less frequent ambulance (p=0.009), arrived to the hospital later than White patients (7.7 hours longer ; p<0.001), had more severe stroke, and had less frequent IV thrombolysis utilization (7% vs 13%; p=0.042). Similarly in the TIA cohort, non-White patients’ utilization of EMS was lower than White patients and their hospital arrival was delayed. In the ICH cohort, non-White patients were younger, had lower frequency of atrial fibrillation, and a non-significant trend towards higher disease severity. The SAH cohort had only 8 non-White patients, 6 of which were transferred to higher level of care hospital within a few hours of arrival, therefore. Importantly, the hospital-based quality metrics such as door-to-CT time, door-to-needle time, and the Joint Commission stroke quality metrics were similar between the two groups. Conclusion: There is a racial disparity in the pre-hospital phase of the stroke chain of survival of non-White patients impacting the IV thrombolysis utilization. The younger age and worse lipid profile and hemoglobin A1C of non-White patients suggest the need for better preventative care starting at young age.

Staphylococcus aureus are commensal bacteria present on skin and mucosae in both humans and animals, but they can also be found in food, water and in various environments. They are also considered a major pathogen having a great morbidity leading to a wide range of infections. They are included in the list of most virulent and antimicrobic resistant bacterial pathogens (ESKAPE, Escherichia coli, Staphylococcus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterococcus faecalis and faecium)) by the Center for Disease Control and Prevention (CDC), and S. aureus is part of the worldwide threat represented by the presence of antimicrobial resistance (AMR). The outcomes of an epidemiological investigation on 26,430 S. aureus isolates from a global public database (NPDIB; NCBI Pathogen Detection Isolate Browser) support the evidence of significant differences in the distribution of isolates and ARGs (Antimicrobial Resistance Genes) clusters among geographical areas of origin and among sources of the isolates. Moreover, the ARGs cluster patterns suggest an association between the isolates from human and animal populations. This outcome and the large diffusion of the pathogens among human and animal populations support the importance of gaining information on the epidemiology of these infections with a One Health approach.

With an estimated 10 million people infected, the deltaretrovirus human T-cell lymphotropic virus type 1 (HTLV-1) is the second most prevalent pathogenic retrovirus in humans after HIV-1. Like HIV-1, HTLV-1 overwhelmingly persists in a host via a reservoir of latently infected CD4+ T cells. Although most patients are asymptomatic, HTLV-1-associated pathologies are often debilitating and include childhood infective dermatitis and adult T-cell leukaemia/lymphoma (ATLL), which presents in mature adulthood and is associated with poor prognosis with short overall survival despite treatment. Curiously, the strongest indicator for the development of ATLL is the acquisition of HTLV-1 through breastfeeding. There are no therapeutic or preventative regimens for HTLV-1. However, antiretrovirals (ARVs), which target the essential retrovirus enzymes, have been developed for and transformed HIV therapy. Since the architectures of retroviral enzyme active sites are highly conserved, some HIV-specific compounds may be active against HTLV-1. Here, we expand on our work showing that integrase strand transfer inhibitors (INSTIs) and some nucleoside reverse transcriptase inhibitors (NRTIs) block HTLV-1 transmission in cell culture. Specifically, we find that dolutegravir, the INSTI currently recommended as the basis of all new combination antiretroviral therapy prescriptions, and the latest prodrug formulation of the NRTI tenofovir, tenofovir alafenamide, also potently inhibit HTLV-1 infection in cell culture. Our results, if replicated in a clinical setting, could see transmission rates of HTLV-1 and future caseloads of HTLV-1-associated pathologies like ATLL dramatically cut via the simple redistribution of already widely available HIV pills to HTLV-1 endemic areas. Considering our findings with the old medical saying ‘it’s better to prevent than cure’, we highly recommend the inclusion of INSTIs and tenofovir prodrugs in upcoming HTLV-1 clinical trials as potential prophylactics.

Introduction: Bone fractures may be the result of high force impact or stress, or a minimal trauma injury as a result of certain medical conditions that weaken the bones, such as osteoporosis, osteopenia, bone cancer, or osteogenesis imperfecta, where the fracture is then properly termed a pathologic fracture. Bone cancer can be primarily or secondary to metastasis. Case presentation: We report a rare case of left humerus fracture in a 59-year-old male patient due to metastatic renal cell carcinoma. Our patient had no important past medical history. He suffered from two months of left arm pain, moderate disability and fever at night. Analgesics consumption resulted in minimal relieve. Trauma history was negative. X-ray of the left arm showed an osteolytic lesion with humerus fracture. Abdominal computed tomography with contrast showed right renal mass.Radical right nephrectomy was performed in addition to alignment nailing of the left humerus fracture with biopsy. Pathology report documented clear cell carcinoma with metastatic bone. The treatment was completed by chemotherapyDiscussion: Secondary bone tumors are metastatic lesions which have spread from other organs, most commonly carcinomas of the breast, lung, and prostate, and rarely from kidney. In some cases, bone metastasis could be the first symptoms of renal cell carcinoma. Conclusion: suspected pathological bone fractures should be investigated completely. It may hide a tumor as a cause.

Study design: Retrospective observational study. Objectives: To evaluate the change in adjacent segment disease (ASD) after hybrid dynamic stabilization with Dynesys-Transition-Optima (DTO). Methods: In 2012–2020, 115 lumbar spinal stenosis patients with spondylolisthesis re-fractory to nonsurgical management received hybrid dynamic stabilization with DTO system in a single medical center from a single neurosurgeon. After excluding those who did not receive L3–L4 dynamic stabilization and L4–L5 transforaminal lumbar interbody fusion fixation and those with incomplete postoperative data (n = 84), the 31 patients studied received follow-up vis-its at 6, 12 and 24 months postoperatively. Radiological assessment applied at the L2–L3, L3–L4 and L5–S1 segments separately included disc height, listhesis distance and angular change while in motion. Implant failure and screw loosening sign were both documented. Results: In the L3–L4 segment, the listhesis distance appeared 1 year after the operation; however, alterations in other segments showed at 6 months. At 2 years, the L3–L4 segment showed significantly less increase in listhesis distance and relatively less disc height reduction than other segments. In motion an-gular change, only the L3–L4 segment had a significant decrease at 2 years. Only the L3–L4 seg-ment maintained negative growth over 2 years in time-dependent assessment of motion angular change. Conclusions: In our study, disc height decreased, listhesis distance increased less and ASD changed later at the index level than the L2–L3 and L5–S1 levels. Angular change was re-duced at the index level while in motion. Although ASD was not significantly prevented, index level degeneration was both minor