Etiological factors involved in myelodysplastic syndrome (MDS) include immunologic, oxidative stress, and inflammatory factors, among others, and these are targets for microRNAs (miRNs). Here, we evaluated whether some miRNs may affect the tumor development comparing untreated and 5-azacitidine (5-AZA) MDS-treated patients. Peripheral blood samples were collected from 20 controls and 24 MDS patients, and selected miRNs related to redox balance and inflammation, including miR-18a, miR-21, miR-34a and miR-146a, were isolated and measured by quantitative real-time polymerase chain reaction (qRTPCR). A differential expression profile of miRNs was detected in untreated MDS patients and 5-AZA group. MiR-18a, miR-21, miR-34a and miR-146a were significantly overexpressed in untreated MDS, compared to controls. However, we did not observe any miRNs profile alteration during the progression of the disease. On the other hand, 5-AZA treatment tends to restore miRNs expression levels. Relating to prognostic risk factors, high risk MDS groups (high IPSS-R, high cytogenetic risk, high molecular risk (HMR) mutations tended to be related with higher expression levels of miR-18a and miR-34a. Higher miRNs expression is correlated with lower glutathione peroxidase activity, while they are related with a higher profile of pro-inflammatory cytokines (IL-2, IL-6, IL-8, TNF-α). Although our study was limited by the low number of MDS patients included, we identified miRNs deregulation involved in the MDS development, that could regulate redox sensors and inflammatory responses. Finally, 5-AZA treatment is related with lower miRNs expression levels in MDS patients.

Balínt Syndrome is an acquired disorder manifesting in the inability to recognize several objects at once (simultagnosia), inaccurate visually guided limb movements despite intact motor function (optic ataxia) and the inability to make accurate voluntary saccades to visual targets despite demonstrating unrestricted range of eye movements (ocular motor apraxia). Here we report the first case of a patient presenting with Balínt Syndrome caused by a platelet-derived growth factor receptor A mutation (PDGFRA)-induced Hypereosinophilic Syndrome (HES).

This study aimed to investigate the efficacy of manual therapy and exercise versus synchronized telerehabilitation with self-manual therapy and exercise in treating Subacromial Pain Syndrome (SPS). Sixty individuals diagnosed with SPS, aged 18-50 years, were randomly assigned to home exercise (HE), manual therapy (MT), and telerehabilitation (TR) groups. Treatment protocols were administered over 8 weeks and included specific exercises and therapy interventions. Out-come measures included Visual Pain Scale (VAS), shoulder range of motion (ROM) via gonio-metric measurements, Quick Disability Arm-Shoulder-Hand Problems Survey (Q-DASH), and patient satisfaction. Results revealed that both MT and TR groups exhibited reduced pain, in-creased ROM, lower Q-DASH scores, and higher patient satisfaction compared to the HE group. However, no significant differences were found between MT and TR groups in pain levels, ROM, Q-DASH scores, or patient satisfaction. The study concludes that both telerehabilitation and manual therapy effectively alleviate pain and are well-received by patients with SPS. Addition-ally, manual therapy demonstrates superiority in enhancing functional levels compared to exer-cise-based interventions. (Registration: NCT05200130)

Predominantly antibody deficiencies (PAD) represent the most common type of primary immu-nodeficiencies in humans, characterized by a wide variation in disease onset, clinical manifesta-tions, complications and outcome. Considering that the prevalence of PAD in Greece is unknown and there is limited knowledge on clinical and laboratory characteristics of affected patients, we conducted a nationwide study, including 153 patients (male/female: 66/87; median age: 43.0 years; range: 7.0-77.0) diagnosed and/or followed-up between April 2007 to September 2023. Furthermore, we classified our cohort into five Groups according to their medical history, im-munoglobulin levels, and CTLA4-mutational status: 123 had common variable immunodeficien-cy (CVID), 12 with CVID-like disease (with a history of a previous B-cell depletion immunother-apy for autoimmune or malignant disease), seven with combined IgA and IgG subclass deficien-cies, five with immune dysregulation syndrome and CTLA4 defects, and six with unclassified hypogammaglobulinemia. We demonstrated a remarkable delay of PAD diagnosis, several years after the onset of related symptoms (median: 9.0 years, range: 0-43.0). Family history of PAD was only 11.8%, with the majority of patients considered sporadic cases. Most patients were diag-nosed in the context of a diagnostic work-up for recurrent infections, or recurrent/resistant auto-immune cytopenias. Interestingly, ten patients (5.6%) had no history of infection, diagnosed due to either recurrent/resistant autoimmunity, or during a work-up of their medical/family history. Remarkable findings included an increased prevalence of lymphoproliferation (60.1%) and atopy (24.2%), while 39 patients (25.5%) developed bronchiectasis and 16 (10.5%) granulomatous dis-ease. Patients with CTLA4 defects displayed a variable clinical phenotype at diagnosis, with four patients diagnosed during a work-up of re-current infections, while one also displayed a massive splenomegaly. Cancer was a common complication in our cohort (25 patients, 16.3%), with B-cell malignancies representing the most common neoplasms (56.7%). Our findings indicate the necessity of awareness about PAD and their complications, aiming for early diagnosis and appropriate management of affected patients

As of now, anthropogenic habitat injury via dissemination of manufactured chemicals is injuring the world’s ecosystems, but doctors have yet to recognize its consequences to humans. Recognition of overt toxicity due to chronic low-dose exposure will open the door to diagnosis, sequential elimination studies, and prescriptions for preventive cure that represent a first step in preventing escalating chronic diseases. This paper offers a diagnostic construct for such use: chronic ambient poisoning. Incorporating it into clinical practice can reduce misdiagnosis of gastro- and near-toxicity that doctors and patients presently suppress rather than remove, and reduce patient co-dependence with proton-pump inhibitors, anxiolytics, and antidepressants—and the thriving “alternative” health industry. This diagnostic elephant-in-the-room is presently missed for reasons of habit (when an ailment is not recognized, it cannot be included in the differential diagnosis) and of poor conduct and interpretation of non-clinical research studies that are taken to mean an absence of evidence is evidence of absence. Moreover, modern methods fail when: the exposure comprises a “daily cocktail” of poisons acting additively, interactively, and cumulatively over a lifetime; when there is no normal, unexposed comparison group; and when absence of a robust etiopathogenetic model disallows inapt statistics. Only patient-led, consultant-informed sequential elimination studies can “peel the onion” of toxicity and its recognition and “preventive cure”. Clinical use of the chronic ambient poisoning diagnosis can thus open the door to stemming and reversing anthropogenic epidemics.

The fatigue delamination damage is one of the most important fatigue failure modes of laminated composite structures. However, the developments of the theoretical framework, mathematical/physical model and numerical simulation of fatigue delamination are still challenging issues, and there is a lack of systematic classification. This article reviews the experimental phenomena of the onset and propagation stage of delamination under fatigue loading, and summarizes the commonly used phenomenological models for laminated composite structures. The research methods, general modeling formulas and development prospects of the phenomenological models are presented in detail. In the light of the analysis of finite element model (FEM) for the laminated composite structures, a number of simulation methods of fatigue delamination crack propagation damage model are carefully classified. Furthermore, within the theoretical framework of strength theory model (SM), fracture mechanics model (FM), damage mechanics model (DM) and hybrid model (HM), the complete procedure, application, capability assessment, advantages and limitations of the models are also discussed in detail. Finally, several valuable suggestions are given for the research interests, and challenging technical problems that need to be overcome on the fatigue delamination prediction of laminated composite structures in the future.

Steel structures, such as bridges, must be continuously maintained. Due to increasing trac loads, design and execution shortcomings, many steel bridges are subject to various types of damage, such as cracks. The bridges must be maintained by crack removal and re-welding the cracks. During this work, the bridge is closed for trac in order to suppress the crack ank movement during welding. As a result, trac loads on other routes are higher, which increases further damage on detour routes and subsequently additional welding work and costs on theses structures. Therefore, the aim is to provide a method that allows welding work on steel structures under running trac, respectively under cyclic loads. First, measurements at a representative steel bridge were conducted to derive gap opening parameters of amplitude and frequency for welding tests under cyclic loads. In a test setup for reproducible and comparable welding tests, specimen were welded under cyclic loads. Deep grinding of the root layer allowed defect-free welding within the range of 0.1 mm amplitude at a frequency of 2 Hz loadings. For such welds, the weld quality and the fatigue strength was comparable to the standard requirements.

In this paper, we present a new stress calculation method for flexible structures, particularly, the tensile armors, and apply it to flexible riser fatigue analysis. The method is based on a 3-dimensional curved bar theory. First, the tensile armor center line was described as a cylindrical helix curve, its bended curve length and bending migration length were derived and studied under different friction scenarios. Second, the tensile and bending stiffness was given with consideration of frictional hysteretic effect, and verified through FEA analysis results. Third, we presented the stress calculation formula for tensile armor under tension and bending load. All stress components are considered, including tensile, bending and shear stresses. Fourth, the method was benchmarked with published experimental results on a flexible prototype tension and bending tests, and comparisons showed general agreements. Fifth, the method is further applied to a 8” flexible riser for fatigue assessment and lifetime extension evaluation, and showed the flexible riser has sufficient remaining fatigue life, and is suitable to continue its service under the current operating conditions. Last, conclusions are drawn. It concluded that the presented tensile armor stress calculation method and modelling techniques are valid for flexible riser fatigue analysis. This method is time efficient, and can be implemented into other multi-scale models for riser dynamic analysis. It is also applicable to other similar helix structure stress analysis, such as wire ropes, submarine hoses, and subsea umbilicals.

Natural cellulose hydrogels have been widely used to enhance mechanical properties. However, existing natural fiber composite hydrogels are not reusable, limiting their potential applications. To address this issue, we designed and prepared a polyvinyl alcohol/glycerol /bamboo microfibril double network tough hydrogel using a simple method. The bamboo microfibril and polyvinyl alcohol form a tight and rigid network through hydrogen bonding, improving mechanical properties. The prepared polyvinyl alcohol/glycerol/bamboo microfibril double network tough hydrogel has the advantages of reusability and fatigue resistance. Furthermore, both the elastic modulus and toughness of the hydrogel increase with increasing bamboo microfibril content. We also demonstrated that the hydrogel can be recast after cyclic compression, maintaining its recyclability, stability, and certain stiffness and toughness. Our study highlights the potential of hydrogels for controllable mechanical properties, fatigue resistance and shows that polyvinyl alcohol/glycerol/bamboo microfibril hydrogel has broad value for plasticity and reuse.

This paper aims to provide an overall review of degradation, damage evolution and fatigue models in the literature of various engineering materials, mostly metals, and composites.

Reliable fatigue design rules affect the proactive identification of safety parameters in aerospace industry. Numerous fatigue crack initiation and propagation models, linear and nonlinear, have been developed for designing purposes or estimation of the remaining life of aging airplanes. Depending on the adopted assumptions, the accuracy varies for different loading histories, loading types, and materials. Semi empirical models are simple but yield significant inaccuracies. Models with better theoretical basis provide better accuracy, but implementation in real conditions is problematic. In the present work, a review of author’s recent fatigue crack initiation and propagation models based on physical mechanisms is presented and improvements are proposed. Verification of the models on test results is provided and discussed.

In Nature, it is common for living plants and non-living plant tissues to consist of materials with anisotropic multilayer and non-homogenous structure. The structure of tissues determines their self-shaping and self-folding capabilities in response to a stimulus in order to activate different functionalities. Predetermined movements are realized according to changes in environmental conditions, which trigger the fibrous anisotropic structure of the plants’ material. In this study, we present the fabrication process of low-cost anisotropic multilayer materials that are capable of realizing complex movements caused by small temperature changes (<40 ^oC). The mismatch in the thermo-mechanical properties between three or more anisotropic thin layers creates responsive materials that alter their shape owing to the developed internal stresses. Isotropic layers can perform only bending movements, whereas anisotropic multilayer materials can perform bending, twisting or complex combined modes. The movements of the material can be controlled by forming anisotropic homogenous metallic strips over an anisotropic polymer. As a result, inexpensive responsive materials can be developed to passively react to a very broad range of thermal requirements. We studied the major parameters that affect the sensitivity of the developed materials, as well as their failure modes and crack formation under thermal fatigue conditions.

Background: Clinical trails have revealed that patients with depression generally accompanied with learning and memory impairment, which critically impact on individual’s health and development. Danggui-Shaoyao-San (DSS), a famous Chinese complex prescription, significantly overcame depression and relieved cognitive disorder based on previous research and publication. However, its effectsand potential mechanism against chronic restraint stress (CRS) remained unknown. Methods: CRS animal model was established and mice were divided to six groups while they were oral administrated with Danggui-Shaoyao-San at doses of 1.25, 2.5 and 5 g/kg for 14 days. Emotional and cognitive performances were detected by behavior tests, meanwhile neural plasticity and its molecular mechanism were examined by Dil staining, western blot and immunofluorescence. Results: DSS treatment dose-dependently improved locomotion ability in open filed test, overcame depression behavior in forced swimming test and elevated plus maze test, enhanced learning and memory ability in Morris water maze test. CRS decreased number of total spines and mushroom spines, while DSS treatment dose-dependently restored these by Dil staining. Expression of BDNF and GluR1 were significantly down-regulated in CRS group, which were significantly normalized by DSS. Conclusions: DSS treatment dose-dependently reversed CRS-induced cognitive impairments by inducing structural remodeling of neurons.

Introduction: Acute compartment syndrome (ACS) is a surgical emergency that requires urgent intervention in order to prevent permanent structural damage and irreversible functional disability. The diagnosis of ACS depends on a high index of suspicion, relying on the following diagnostic criteria commonly known as the 5 Ps; Pain, Paresthesia, Paralysis, Pallor, and Pulse-lessness. When the diagnosis is uncertain, intracompartmental pressure greater than 30 mmHg is suggestive of ACS. Case Presentation: We report a case of an underdiagnosed ACS, with a lack of classical presentation in a thirty-seven-years-old male patient with a history of myopathy. The patient was admitted to the emergency room due to direct trauma to his right hip, without a significant Visual Analogue Score. On his hip radiograph a subtrochanteric fracture of the right femur was demonstrated. An additional masked ipsilateral subcapital fracture was detected during the operation. The diagnosis of ACS was made during the operation while relying on the clinical appearance of the thigh and the clinical findings during surgery. Fasciotomies were performed, and open reduction with internal fixation via Proximal Femoral Nail was done. The diagnosis of ACS was confirmed later on, by the biopsy results. Conclusion: This case suggests that myopathy can mask the classical presentation of ACS. Furthermore, the extent of pain complaints and accompanying paresthesia cannot be relied on in this regard and other clinical features should be considered in order to diagnose ACS.

Caudal regression syndrome (CRS) is a congenital abnormality characterized by an incomplete development of the spinal cord (SC) and other abnormalities. We studied a 9-months old CRS child presenting: interruption of SC at L2-L3 level, sacral agenesis, lack of innervation of the inferior limbs (flaccid paraplegia) and neurogenic bladder and bowel. Given the effects of growth hormone (GH) on the proliferation, differentiation and migration of neural stem cells (NSCs), we treated him with GH and rehabilitation, trying to induce the recovery of main sequelae. GMFM-88 test score was 12.31%. After a blood analysis, GH treatment (0.3 mg/day, 5 days/week, 3 months and then 15 days without GH) and rehabilitation commenced. This protocol was followed during 5 years, being the last GH dose 1 mg/day. Blood analysis and physical exams were performed every 3 months initially and every 6 months later. Six months after commencing the treatment GMFM-88 score increased to 39.48%. Responses to sensitive stimuli appeared in most of the territories explored; 18 months later sensitive innervation was complete and the patient moved any muscle over the knees and controlled his sphincters. Three years later he walked with the help of canes, there was plantar flexion and GMFM-88 score was 78.48%. In summary, GH plus rehabilitation may be useful for innervating distal territories, below the level of the incomplete spinal cord in CRS. Most likely, GH acts on ependymal SC NSCs, as the hormone does in the neurogenic niches in the brain.

ME/CFS (Myalgic Encephalomyelitis / Chronic Fatigue Syndrome) is a chronic, complex, heterogeneous disease that affects millions and lacks both diagnostics and treatments. Big data, or the collection of vast quantities of data that can be mined for information, has transformed the understanding of many complex illnesses like cancer (1,2) and multiple sclerosis (3,4), by dissecting heterogeneity, identifying subtypes, and enabling the development of personalized treatments. It is possible that big data can reveal the same for ME/CFS. Solve M.E. developed and launched the You + ME Registry to collect longitudinal health data from people with ME/CFS, people with Long COVID (LC) and control volunteers using rigorous protocols designed to harmonize with other groups collecting data from similar groups of people. The Registry is an invaluable resource because it integrates with a symptom tracking app, as well as a biorepository, to provide a robust and rich dataset that is available to qualified researchers. Accordingly, it facilitates collaboration that may ultimately uncover causes and help accelerate the development of therapies.

The plate heat exchanger (PHE) is a component that provides heat to be transferred from hot water to domestic cold water without mixing them with high efficiency. Over the lifetime of the PHE, cyclic pressures act on the brazing points and the plates, and this may lead to fatigue failure. The fatigue behaviour of the PHE, designed by using copper-brazed 316L stainless steel, was investigated in this study. First, the fatigue tests under the load ratio R = 0.1 were performed on the Vibrophore 100 testing machine to obtain the S-N curve of the analysed brazed joint. Based on the obtained experimental results, an appropriate material model of the analysed brazed joint has been created, which was validated with numerical calculation in the framework of a program code Ansys. A validated material model was then used for the subsequent numerical analysis of PHE. In order to carry out a numerical calculation using the finite element method (FEM), a 3D model of the heat exchanger was created based on the previous scanning of PHE-geometry. Thereafter, the geometry was parameterised, which allowed us to perform parametric simulations (monitoring different responses depending on the input geometry). Numerical simulations were carried out in the framework of the Ansys software, whereby the obtained results were analysed, and the responses were appropriately characterised according to previously determined load cases.

Current pharmacological treatments of Fibromyalgia (FM) are merely symptom palliative, as clinical trials have so far failed to provide overall benefits without associated harms. Polypharmacy often leads to patient´s health deterioration and chronic drug use to an eventual lack of patient´s response. Emerging evidence support that physiotherapy treatments based on mechanical triggers improve FM symptoms and therefore could be used for therapeutic purposes by themselves, or in combination with current pharmacological treatments, as part of integrative medicine programs. However, a paucity of studies rigorously and systematically evaluating this possibility exists. This study uses scores from validated standardized questionnaires, algometer pressure point threshold (PPT) readings and responses from a custom self-developed questionnaire to determine the impact of a pressure-controlled manual protocol on FM hyperalgesia/allodynia, fatigue and patient´s quality of life. The results show that patient´s baseline sensitivity to pain inversely correlates with treatment response in FM. Moreover, patients presenting comorbid ME/CFS do not seem to respond to the applied therapy as those presenting FM only. Thus, pre-treatment PPTs and ME/CFS comorbidity may serve as indicators to predict patient´s response to physiotherapy programs based on mechanical triggers, as the one evaluated here. These unexpected findings grant further explorations including the study of gene expression profiles associating to patient´s treatment response in the blood collection of samples generated by this study.

Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by a defect in the phagocytic function of the innate immune system owing to mutations in genes encoding the five subunits of the nicotinamide adenine dinucleotide (NADPH) oxidase enzyme complex. This review aimed to provide a comprehensive approach to the pathogens associated with chronic granulomatous disease (CGD) and its management. The topics covered included common pathogens infecting CGD patients, granulomas, and CGD-related infectious diseases, including invasive aspergillosis, Mulch pneumonitis, and liver abscesses. In addition, we also covered the differential diagnosis of CGD and its management. Patients with CGD, often children, have recurrent life-threatening infections and may develop infectious or inflammatory complications. The most common microorganisms observed in the patients with CGD are Staphylococcus aureus, Aspergillus spp, Candida spp, Nocardia spp, Burkholderia spp, Serratia spp, and Salmonella spp. Triple-dose antimicrobial prophylaxis with empiric regimens is recommended. Therefore, therapeutics against this disease must be optimised, considering the lack of curative therapies and the long-term side effects of prophylactic regimens. Consequently, allogeneic haematopoietic stem cell transplantation from a human leukocyte antigen-identical donor has been proven to cure CGD.

Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by a defect in the phagocytic function of the innate immune system owing to mutations in genes encoding the five subunits of the nicotinamide adenine dinucleotide (NADPH) oxidase enzyme complex. This review aimed to provide a comprehensive approach to the pathogens associated with chronic granulomatous disease (CGD) and its management. The topics covered included common pathogens infecting CGD patients, granulomas, and CGD-related infectious diseases, including invasive aspergillosis, Mulch pneumonitis, and liver abscesses. In addition, we also covered the differential diagnosis of CGD and its management. Patients with CGD, often children, have recurrent life-threatening infections and may develop infectious or inflammatory complications. The most common microorganisms observed in the patients with CGD are Staphylococcus aureus, Aspergillus spp, Candida spp, Nocardia spp, Burkholderia spp, Serratia spp, and Salmonella spp. Triple-dose antimicrobial prophylaxis with empiric regimens is recommended. Therefore, therapeutics against this disease must be optimised, considering the lack of curative therapies and the long-term side effects of prophylactic regimens. Consequently, allogeneic haematopoietic stem cell transplantation from a human leukocyte antigen-identical donor has been proven to cure CGD.

Background: It has been reported that general adiposity in adulthood and early adulthood, and greater height may increase the risk of almost all types of lympho-haematopoietic cancers while a study done in MD Anderson found that obesity and adult weight gain are independent risk factors for CML however no study evaluated the role of obesity in the disease progression while more studies investigate the impact of translocation types. Method: We conducted a retrospective analysis of the files of 37 patients being treated in our center for CML in chronic phase (CMP-CP) with known BCR-ABL1 breakpoints, Results: patients’ management and response assessment was done based on ELN 2013 guidelines. Analysis is done based on two main groups, obese vs normal BMI, and then based on BCR-ABL1 transcripts: e13a2 vs e14a2. Although the number of cases is limited, in the patient-cohort studied an e14a2 BCR-ABL1 transcript type / normal body weight was associated with an inferior outcome when compared to e13a2 transcript / obesity groups Conclusion: our finding suggest the need to enlarge the series to better evaluate a potential role of altered metabolism and/or specific transcripts in the response to TKI in CML.

Individuals with metabolic syndrome have increased risk for developing health conditions, in-cluding cardiovascular diseases and stroke. Modifiable risk factors, such as exercise and diet, are key components in the prevention and control of metabolic syndrome. Specifically, dietary pat-terns and habits are extremely successful in controlling more than one of the metabolic syn-drome risk factors. Meal timing and frequency have been associated with type 2 diabetes, cardi-ovascular diseases, and other chronic conditions. However, there is limited evidence linking metabolic syndrome to meal timing and meal frequency. This review summarizes and discusses how meal timing and frequency impact metabolic outcomes in adults.

The European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE) was established after a successful grant application to the European Cooperation is Science and Technology (COST). This network aimed to assess the existing knowledge and/or experience on health care delivery for people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in the European countries and worldwide, and to enhance coordinated research and health care provision in this field. The EUROMENE proposal, was based on the establishment of interrelated working groups (WGs), where the participants contributed with specific knowledge and viewpoints according to their specialties and/or areas of interest. In this paper we outline the work of a multidisciplinary team of researchers, including epidemiologists, clinicians, statisticians, biomedical scientist and heath economists, who set out their recommendations to guide data acquisition for ME/CFS research, aiming to standardise data collection and improve epidemiological research.

Background: DICER1, cancer predisposition syndrome (CPS), seems to escape timely diagnosis in pediatric patients. Case report 1: A 16-year-old female patient was referred to the endocrinology ward due to a large goiter. Her medical history indicated normal sexual maturation, with menarche occurring at 13.5 years. Over the past 2.5 years, she developed pronounced androgenic symptoms, including a deepened male voice, facial, back and neckline acne, hirsutism, and menstrual irregularities leading to secondary amenorrhoea. A thyroid ultrasound identified a multinodular goiter with cystic-solid lesions containing calcifi-cations. An abdominal ultrasound identified a 5.7x6.9 cm solid mass in the right adnexal region, displacing the uterus to the left. Histopathological examination confirmed a Sertoli-Leydig cell tumor. The patient was subjected to total thyroidectomy. Histopathology revealed benign follicular cell-derived neoplasms. Thyroid follicular nodular disease was diagnosed bilaterally. DNA analysis using NGS, confirmed by the Sanger method, revealed a pathogenic heterozygotic variant c.2953>T [p.Gln985*] in exon 18 of DICER1 gene. Case report 2: A 12-year-old male patient was admitted to the pediatric surgery unit due to a 33 ml goiter. A month prior to admission, the patient discovered a palpable nodule in his neck, accompanied by hoarseness. An ultrasound revealed a multinodular goiter. Molecular analysis revealed a pathogenic heterozygotic variant c.2782C>T [p.Gln928Ter] in exon 17 of DICER1 gene. Subsequently, a total thyroidectomy was performed, and histopathological examination revealed thyroid follicular nodu-lar disease bilaterally. Conclusion: Multinodular goiter, although rare in pediatric population, when accompanied by characteristic ultrasound and histopathological features, and by additional features such as androgen excess, warrants exclusion of DICER1 syndrome.

In this paper, we investigate the effects of mean stress, multiaxial loading, and residual stresses on the fatigue life of springs. We study the fatigue life of a homogeneously stressed material subjected to cyclic loading with nonzero mean stress. Traditional methods for estimating fatigue life are based on Goodman and HAIGH diagrams. The formal analytical descriptions, namely "stress-life" and "strain-life" approaches, are found to be more suitable for the numerical methods. The fatigue analysis method described above, which describes crack growth per cycle, is extended. The extensions allow consideration of the mean stress of a load cycle. Closed-form expressions for crack length versus number of cycles are derived. The complementary effects on the fatigue life of springs, which ultimately have a significant influence on the fatigue life of springs, are summarized. For the proposed unified fatigue life functions, the ranges for the stress loading factor are extended by introducing the effective stress intensity. The solution leads to the factor range for the effective stress intensity, the effective mean value of the stress intensity factor and the effective stress ratio. The developed method assumes the homogeneous stress state in the whole spring element. For the non-homogeneously loaded structural elements, the weak-link concept is applied to account for fatigue.

Little is known about how recreational triathletes prepare for an Olympic distance event. The aim of this study was to identify the training characteristics of recreational-level triathletes within the competition period and assess how their preparation for a triathlon influences their health and their levels of fatigue. During the 6 weeks prior to an Olympic distance triathlon, and the 2 weeks after, 9 recreational athletes (5 males, 4 females) completed a daily training log. Participants answered the Daily Analysis of Life Demands Questionnaire (DALDA), the Training Distress Scale (TDS), and the Alberta Swim Fatigue and Health Questionnaire weekly. The Recovery-Stress Questionnaire (REST-Q) was completed at the beginning of the study, on the day before the competition, and at the end of week 8. Training loads were calculated using session-based rating of perceived exertion (sRPE). The data from every week of training was compared to week 1 to determine how athletes’ training and health changed throughout the study. No changes in training loads, duration, or training intensity distribution were seen in the weeks leading up to the competition. Training duration was significantly reduced in week 6 (p=0.041, d = 1.58, 95% CI = 6.9, 421.9), while the number of sessions was reduced in week 6 (Z=2.32, p=0.02, ES = 0.88) and week 7 (Z = 2.31, p=0.02, ES = 0.87). Training was characterized by large weekly variations in training loads and a high training intensity. No significant changes were seen in the DALDA, TDS, or REST-Q questionnaire scores throughout the 8 weeks. Despite large spikes in training load and a high overall training intensity, these recreational-level triathletes were able to maintain their health in the 6 weeks of training prior an Olympic distance triathlon.

Fatigue remains a challenge especially for high end metal AM parts and materials. From a design perspective, the fatigue limit of an AM solution can be improved upon by optimizing the manufacturing process for a certain material and part. In addition, improved accuracy of design methodologies aids in capturing the features critical for fatigue and quantifies their significance to desired part lifetime as well as providing a basis for their avoidance. In current work we present an overall concept merging thermomechanical process and powder bed solidification modeling to micromechanical analysis of fatigue of the resulting material microstructure. Material features critical to fatigue, particularly surface roughness, internal defects such as porosity and cracks and on the other hand inclusions, can be assessed directly on the basis of AM part microstructure with respect to the resulting fatigue limit. Case analyses consist of maraging steel and nickel alloys. The overall scheme provides a basis for optimization of metal AM solutions against fatigue and multiscale modeling founded basis for fatigue design.

Using the culture-work-health model, this study investigates the factors influencing the quality of life of maritime workers. This study conducted a survey of 320 maritime workers who have experience living and working on a ship for more than six months. This self-administered questionnaire included questions on organizational culture and support, self-efficacy, perceived fatigue, as well as the quality of work life. Organizational culture and self-efficacy were identified as factors affecting the quality of work life, while organizational support was found to have an indirect effect after passing through self-efficacy and perceived fatigue. The final model accounts for 63.1% of the variance in maritime workers’ quality of life. As such, this study shows that self-efficacy is important for the quality of life of maritime workers, having both direct and indirect effects. Moreover, organizational support may prove the primary intervention point for relieving perceived fatigue and enhancing self-efficacy, thus improving the quality of work life.

In chronic myeloid leukemia (CML), a clonal proliferative disorder of granulocytic lineage, the 90%‐95% of cases are characterized by t(9;22) (q34.1;q11.2) translocation, leading to the Philadelphia chromosome (1). Rarely, CML patients directly present a blast crisis, mostly of myeloid origin (2, 3). Herein, we describe one rare CML case, showing an unusual early T lymphoid blastic crisis.

Congenital Disorders of Glycosylation (CDG) are a heterogenous group of primarily autosomal recessive mendelian diseases caused by disruptions in the synthesis of lipid linked oligosaccha-rides and their transfer to proteins. CDGs affect multiple organ systems and vary in presentation, even within families. Here we describe a chemically induced mouse mutant, tvrm76, with early onset photoreceptor degeneration. The recessive mutation was mapped to Chromosome 9 and as-sociated with a missense mutation in the Dpagt1 gene encoding UDP-N-acetyl-D-glucosamine:dolichyl-phosphate N-acetyl-D-glucosaminephosphotransferase (EC 2.7.8.15). The mutation is predicted to cause a substitution of aspartic acid with glycine at residue 166 of DPAGT1. Increased expression of Ddit3, and elevated levels of HSPA5 (BiP) sug-gest the presence of early-onset endoplasmic reticulum (ER) stress. These changes were associated with induction of photoreceptor apoptosis in tvrm76 retinas. Mutations in human DPAGT1 cause Myasthenic Syndrome 13 and severe forms of Congenital Disorder of Glycosylation Type Ij. In contrast, Dpagt1tvrm76 homozygous mice present with congenital photoreceptor degeneration without overt muscle or muscular junction involvement. Our results suggest the possibility of DPAGT1 mutations in human patients that present primarily with retinitis pigmentosa with little or no muscle disease. Variants in DPAGT1 should be considered when evaluating cases of non-syndromic retinal degeneration.

The aim of our study was to assess university students’ sleep quality and fatigue before and during the academic exam period and identify potential associated factors. A Web-based survey was completed by 940 students of 20 different Tertiary Institutions including demographics, sleep habits, exercise, caffeine, tobacco, alcohol use, subjective sleep quality (Pittsburgh Sleep Quality Index - PSQI) and fatigue (Fatigue severity scale – FSS) at the beginning of semester and at examination period. During exam period, PSQI (8.9 vs 6.1, p&lt;0.001) and FSS scores (36.9 vs 32.7, p&lt;0.001) were significantly elevated compared to pre-exam period. Increase of PSQI score was associated with age (β=0.111, p=0.011), presence of chronic disease (β=0.914, p=0.006), and depressive symptoms (β=0.459, p=0.001). Increase of FSS score was associated with female gender (β=1.658, p&lt;0.001), age, (β=0.198, p=0.010), increase in smoking (β=1.7, p=0.029), coffee/energy drinks consumption (β=1.988, p&lt;0.001), decreased levels of physical exercise (β=1.660, p&lt;0.001), and depressive symptoms (β=2.526, p&lt;0.001). In conclusion, our results show that sleep quality and fatigue are affected in university students during exam periods. Potential factors were identified which may lead to development of strategies for better quality of sleep, and wellbeing.

Background: Obesity among pregnant women is common, and their offspring are predisposed to obesity, insulin resistance, and diabetes. Circulating metabolites that are related to insulin resistance and are associated with this decreased tissue-specific uptake are unknown. Here, we assessed metabolite profiles in elderly women and who were either female offspring from obese mothers (OOM) or offspring of lean mothers (OLM). Metabolic changes were tested for associations with metrics for insulin resistance. Methods: 37 elderly women were separated into an elderly offspring from obese mothers (OOM; n = 17) and elderly offspring from lean/normal weight mothers (OLM; n = 20) groups. We measured plasma metabolites using 1H-NMR and also insulin-dependent tissue specific glucose uptake in skeletal muscle were assessed. Associations were made between metabolites and glucose uptake. Results: Compared to the OLM group, we found that the 22:6 docosahexaenoic acid percentage of the total long chain n-3 fatty acids (DHA/FA) was significantly lower in OOM (P = 0.015). DHA/FA associated significantly to skeletal muscle GU (P = 0.031) and M-value in the OLM group only (P = 0.050). Conclusions: DHA/FA is associated with insulin-dependent skeletal muscle glucose uptake and that this association is significantly weakened in the offspring of obese mothers.

The objective of this study was to analyze the effects of a pulmonary telerehabilitation (TR) program in young adults with post-COVID-19 syndrome. The information of sixteen students' medical files were analyzed and allocated to one of two groups (control=CG/experimental=EG). Twelve TR sessions were performed distantly and asynchronously at the EG patients' homes during 4-weeks. The program included diaphragmatic pattern breathing and aerobic exercises. The parameters: i) vital signs (oxygen saturation "SpO2", heart rate "HR", respiratory rate "RR" and blood pressure "BP"; ii) physical capacity “Sit-to-stand test”; iii) cardiorespiratory capacity “6-Minute Walk Test”; and iv) perceived effort "Borg scale" were assessed in both groups. The statistical analyses showed a significant decrease of RR and HR (p < 0.012) accompanied by a significant increase in SpO2 (p < 0.042), physical (p < 0.012) and respiratory (p < 0.028) capacity. The perceived effort decreased significantly in both groups (CG: p < 0.006; EG p < 0.001) only for physical but not for cardiorespiratory capacity (p < 0.106). There were no statistical changes registered in BP (p > 0.05). The current study suggests that a TR program that involves breathing and aerobics exercises is feasible and effective in treating post-COVID-19 syndrome in young patients.

The fixed stroke fatigue test can not simulate the real load condition of the landing gear, and the variable stroke fatigue test has increasingly become the mainstream. A modular test device for fatigue test for aircraft landing gears was designed, the automatic control of the buffer stroke was realized with ectopic displacement control technology effectively, the horizontal loading cylinder could follow the wheel axis actively with the displacement active control technology, follow-up loading along the vertical direction was realized through constructing a polar coordinate system and making the load line automatic alignment, a split-type dummy wheel was designed to improve the loading accuracy, a booster cylinder was designed to realize the control loading of high pressure combined with the hydraulic control system. The test shows that the technical scheme meets the design requirements, and the fatigue test was completed successfully. The device for landing gear variable stroke fatigue testing can be applied to other landing gear static / fatigue tests.

In the Netherlands, the assessment of existing prestressed concrete slab-between-girder bridges showed that the thin, transversely prestressed slabs may be critical for static and fatigue punching when evaluated using the recently introduced Eurocodes. On the other hand, compressive membrane action increases the capacity of these slabs and changes the failure mode from bending to punching shear. To improve the assessment of the existing prestressed slab-between-girder bridges in the Netherlands, two 1:2 scale models of an existing bridge, the Van Brienenoord Bridge, were built in the laboratory and tested monotonically as well as under cycles of loading. The result of these experiments is: 1) the static strength of the decks, showing that compressive membrane action significantly enhances the punching capacity, and 2) the Wöhler curve of the decks, showing that compressive membrane action remains under fatigue loading. The experimental results can then be used for the assessment of the most critical existing slab-between-girder bridge. The outcome is that the bridge has sufficient punching capacity for static and fatigue loads, and thus that the existing slab-between-girder bridges in the Netherlands fulfil the code requirements for static and fatigue punching.

The use of high strength to weight ratio laminated composites is emerging in marine industry and applications as a very efficient solution for improving productivity. Nevertheless, delamination between the layers is a limiting factor for the wider application of laminated composites, as it reduces the stiffness and strengths of the structure. Interleaving nanofibrous mats between layers of composite laminates has been proved to be an effective method for improving composites delamination resistance. This paper aims to characterize the effect of interleaved nanofiber on mode I interlaminar properties and failure mechanisms when subjected to static and fatigue loadings. For this purpose, virgin and nanomodified woven laminates were subjected to Double Cantilever Beam (DCB) specimens. Static and fatigue tests were performed and the tests were monitored by acoustic emission technique. The mechanical results showed a 130% increase of delamination toughness for nanomodified specimens in the static loadings and more crack growth resistance in the fatigue loading. The AE results revealed that different type of failure mechanisms was the cause of these improvements for the modified specimens compared with the virgin ones.

Lyme disease and associated co-infections are increasing worldwide and approximately 20% of individuals develop chronic Lyme disease (CLD)/Post-Treatment Lyme Disease Syndrome (PTLDS) despite early antibiotics. A 7–8-week protocol of double dose dapsone combination therapy (DDDCT) for CLD/PTLDS results in symptom remission in approximately 50% of patients for one year or longer, with published culture studies indicating higher doses of dapsone demonstrate efficacy against resistant biofilm forms of Borrelia burgdorferi. The purpose of this study was therefore to evaluate higher doses of dapsone in the treatment of resistant CLD/PTLDS and associated co-infections. Twenty-five patients with a history of Lyme and associated co-infections, most of whom had ongoing symptoms despite several courses of DDDCT, took one or more courses of high dose pulsed dapsone combination therapy (200 mg dapsone X 3-4 days and/or 200 mg BID x 4 days), depending on persistent symptoms. The majority of patients noticed sustained improvement in 8 major Lyme symptoms, including fatigue, pain, headaches, neuropathy, insomnia, cognition, and sweating, where dapsone dosage, not just treatment length, positively affected outcomes. High dose pulsed dapsone combination therapy may represent a novel therapeutic approach for the treatment of resistant CLD/PTLDS, and should be confirmed in randomized, controlled clinical trials.

Vitamin D has important anti-inflammatory, anti-microbial properties and plays a central role in host immune response. Due to the crucial role of the kidneys in the metabolism of vitamin D, patients with chronic kidney disease (CKD), are prone to vitamin D deficiency. The resultant reduction in the production of calcitriol, the activated form of vitamin D in patients with CKD is responsible for exacerbating the existing renal impairment and periodontal inflammation. Recent evidence suggests a bidirectional, causal relationship between periodontitis and renal functional status. Both conditions have shared pathophysiologic mechanisms including oxidative stress, increases in the systemic inflammatory burden and impaired host response. This review explores the association between vitamin D, CKD and periodontitis. The review summarises the current evidence base for the classical and non-classical vitamin D metabolic pathways, the biological mechanisms linking vitamin D deficiency, CKD and periodontitis, as well as the bidirectional relationship between the two chronic inflammatory conditions. Finally, the paper explores the impact of vitamin D deficiency on CKD, periodontitis, and related co-morbidities.

In Chronic Myeloid Leukemia (CML) patients, CD34+/CD38-/CD26+ cell population represents a “CML specific” Leukemia Stem Cell (LSC) compartment. Indeed, preliminary studies showed that the expression of CD26 discriminates bone marrow CML Leukemic Stem Cells (LSCs) from nor-mal Hematopoietic Stem Cells (HSCs) or from LSCs of other myeloid neoplasms. We were first to demonstrate that at diagnosis CD34+/CD38-/CD26+ cells are easily measurable also in Peripheral Blood (PB) and that residual circulating CD26+LSCs persist, with a fluctuating trend, in most pa-tients in optimal response during treatment with Tyrosine Kinase Inhibitors (TKIs) and even after successful TKI discontinuation. These data corroborate and confirm the possibility of using flow-cytometry CD26+ evaluation as an important diagnostic tool that, combined with molecular biology and cytogenetic, could provide a rapid diagnosis of Chronic Phase (CP) CML starting from a simple PB sample. Yet, few data are available regarding the behavior of CD26+LSCs during Accelerated Phase (AP) or Blast Phase (BP) CML and the role, if any, this peculiar staminal cell compartment may play in disease progression. In the present study we compared the presence and phenotypic characteristics of circulating CD26+LSCs in CP CML patients at diagnosis, during AP and in cases of progression to lymphoid BP, inquiring a possible role of these cells during dis-ease evolution.

: This article was not intended to be a complete report of a standard clinical trial. It is a report of the outcomes of preliminary data for validation of the CMECD procedure (Coletti Method of EMG ChemoDenervation) protocol for the treatment of chronic pain resulting from chronic muscle spasm. Methods are here detailed on how to approach the patient with chronic pain, identify the presence of chronic muscle spasm, undertake the treatment protocol and how to perform the follow up process to confirm that chronic pain secondary to chronic muscle spasm was the accurate diagnosis. Furthermore, this article presents the results of a cohort of more than 90 patients treated by the CMECD procedure regarding location and duration of prior pain, prior treatment strategies, degree of success in resolving pain and duration of relief. Outcome data consisting of patient and staff reporting of specific situations in which the chronic pain treatment was successful has been included to help establish the “believability” of outcome successes and to elucidate the potential life altering effects of successful treatment of chronic pain secondary to chronic muscle spasm. This article will hopefully increase the interest in this treatment protocol and increase the chance that a classical international clinical trial will be undertaken.

The progressive reappearance of the Zika virus (ZIKV) infection since October 2013 and its circulation in >70 countries and territories (from French Polynesia to Brazil and other countries in the Americas, with sporadic spread in Europe and the East) has long been reported as a global public health emergency. ZIKV is a virus transmitted by arthropods (arboviruses), mainly by Aedes mosquitoes. ZIKV can also be transmitted to humans through mechanisms other than vector infection such as sexual intercourse, blood transfusions, mother-to-child transmission. The latter mode of transmission can give rise to a severe clinical form called Congenital Zika Syndrome (CZS) which can result in spontaneous abortion or serious pathological alterations in the fetus such as microcephaly, neurological and orofacial anomalies. In this study, beside a succinct overview of the etiological, microbiological, epidemiological aspects and modes of transmission of Zika virus infection, we have focused our attention on the pathogenetic and histopathological aspects in pregnancy and the pathogenetic and molecular mechanisms that can determine microcephaly, and consequently the clinical alterations, typical of the fetus and newborns, in a subject affected by CZS.

This work aims at improving surface integrity and LCF life of machined Inconel 718. The correlation between the LCF life of Inconel 718 and various states of machined surface integrity is explored. In this paper, the surface integrity of Inconel 718 specimens is enhanced by low plasticity burnishing (LPB). The LCF life with different surface integrity specimens is predicted by micro-macro finite element method (FEM). Firstly, the LCF specimens with different surface integrity are machined by turning (turned specimen), polishing (matrix specimen) and LPB process (LPBed specimen). Secondly, the LCF experiment is carried out to reveal the effect of surface integrity on LCF life. Finally, the LCF micro-macro FEM model is proposed to predict the LCF of machined Inconel 718 specimens. The representative volume element (RVE) model is established based on the measured surface integrity and microstructure of Inconel 718 specimens. The effect of surface integrity on LCF life is transformed to equivalent load. The micro-macro FEM model combined with Tanaka-Mura dislocation crack initiation theory and extended finite element method (XFEM) is applied to predict the LCF life the machined specimens. The study results show that the LCF life of LPBed specimens can be improved by 90.5% and 36.1% compared with that of turned specimens and polished matrix specimens, respectively. The errors between FEM prediction results and experimental results are 13.1%, 9.2% and 12.2%, respectively. The proposed micro-macro FEM model could be utilized to predict the LCF life of Inconel 718 with different surface integrity, and further to apply the LCF life prediction in industry.

Although the Orthotropic steel decks (OSDs) have been widely used in the construction of long-span bridges, there are frequently reported fatigue cracks after years of operation, and the bridge deck overlay also presents severe damage due to OSD crack-induced stiffness reduction. The ultra-high performance concrete (UHPC), recognized as the most innovative cementitious composites and the next generation of high-performance materials, shows high strength, ductility, toughness and well performance on durability. After its first application to the OSD bridge in early 2000s, the orthotropic Steel-UHPC composite deck has been comprehensively studied worldwide. This review will summarize some important studies and findings on behavior and fatigue performance of orthotropic steel-UHPC composite deck. The existing studies and engineering application indicate that such deck system presents good bending behavior and high fatigue performance. The failure mode of shear studs in UHPC layer is dominated by shear fractures. The cracking of UHPC layer shall consider the superposition effect of stress from both the whole bridge structure and local decks. While some reasonable structural details in the traditional OSD may not work for the orthotropic steel-UHPC composite deck. It is recommended to evaluate the stress behavior and structural parameters, as well as fatigue life by conducting the field test under in-service traffic conditions.

This study explored the development of neuromuscular fatigue responses during progressive cycling exercise. The sample comprised 32 participants aged 22.0 ± 0.54 years who were assigned into three groups: endurance-trained group (END, triathletes, n = 10), strength-trained group (STR, body-builders, n = 10), and control group (CON, recreationally active students, n = 12). The incremental cycling exercise was performed using a progressive protocol starting with a 3 min resting measurement and then 50 W workload with subsequent constant increments of 50 W every 3 minutes until 200 W. Surface electromyography (SEMG) of rectus femoris muscles was recorded during the final 30 s of each of the four workloads. During the final 15 s of each workload, participants rated their overall perception of effort using the 20-point RPE scale. Post-hoc Tukey’s HSD testing showed significant differences between END and STR groups in MF and MPF across all workloads (p < 0.001 and p < 0.01, respectively). Athletes from END group had significantly lower AEMG responses than those from STR (p = 0.0093) and CON group (p = 0.0006). Increasing RPE points from 50 to 200 W were significantly higher in STR than in END group (p < 0.001). In conclusion, there is a significant variation in neuromuscular fatigue profiles between athletes with different training backgrounds when a cycling exercise is applied. The approximately linear trend of the SEMG and RPE values of both groups of athletes with increasing workload support the increased skeletal muscle recruitment with perceived exertion or fatiguing effect.

The fatigue life of welded joints under cyclic loading is a complex process that can be roughly divided into fatigue crack initiation, crack propagation and final fracture. Usually, these phases are evaluated separately. Several methods are available to estimate the extent of the different phases in welded components, such as stress-based fatigue concepts for crack initiation or linear elastic fracture mechanics for crack propagation; however, distinguishing these phases in welded components is a complex procedure and often relies on assumptions such as transition crack sizes. The objective of this study is to investigate the relationship between fatigue crack initiation and propagation in welded joints using artificially notched specimens with welded joints characteristics of different notch acuity (different radii and opening angle). The experiments show that the investigated relationship basically depends on the notch acuity, the load level and the stress ratio.

Background: Depending on the phase of the menstrual cycle the athlete is in, some kinetic, physiological and fatigue variables will show differences. The aim of this study is to analyze whether there are changes in these variables over the course of the menstrual cycle. Methods: Eight regular female runners and triathletes performed a maximal treadmill test, as well as a submaximal test (6’ stages at 50%, 60% and 80% of maximal aerobic speed) in each of the phases of the menstrual cycle: bleeding phase (day 2.4 ± 0.7), follicular phase (day 10.4 ± 2.2) and luteal phase (day 21.8 ± 2.1). Running dynamics were measured (using RunScribe) at the end of each test, as were lactate concentration, heart rate and fatigue (evaluated on a scale of 0 to 5). Results: Higher shock (G) values were recorded in the bleeding phase and higher vertical spring stiffness (kN/m) in the follicular phase. The phase of the menstrual cycle had a significant effect on average and peak heart rate, which was significantly higher in the follicular phase. Conclusions: Higher vertical spring stiffness was observed in the follicular phase, as well as higher peak and average heart rate.

In this paper, the fatigue response of Fused Filament Fabrication (FFF) Acrylonitrile butadiene styrene (ABS) parts is studied. Different building parameters (layer height, nozzle diameter, infill density, and printing speed) were chosen to study their influence on the lifespan of cylindrical specimens according to a design of experiments (DOE) using the Taguchi methodology. The same DOE was applied on two different specimen sets using two different infill patterns: rectilinear and honeycomb. The results show that infill density is the most important parameter for both studied patterns. The specimens manufactured with the honeycomb pattern show longer lifespans. The best parameter set associated to that infill was chosen for a second experimental phase, in which the specimens were tested under different maximum bending stresses to construct the Wöhler curve associated to this 3D printing configuration. The results of this study are useful to design and manufacture ABS end-use parts that are expected to work under oscillating periodic loads.

Plasma treatment of soft polymers is the promising technique to improve biomedical properties. The response to the deformation of such materials is not yet clear. Soft elastic polyurethane treated with plasma immersion ion implantation is subjected to fatigue uniaxial loading (50000 cycles, frequency – 1 Hz, strain amplitude – 10, 20, 40%). The influence of the strain amplitude and the plasma treatment regime on damage character is discussed. Surface defects are studied in unloaded and stretched states of the material. As a result of fatigue loading, transverse cracks (with closed overlapping edges as well as with open edges deeply propagating into the polymer) and longitudinal folds which are break and bend inward, appear on the surface. Hard edges of cracks cut the soft polymer which is squeezed from the bulk to the surface.

Vascular calcification (VC), is a common complication in patients with chronic kidney disease and increases mortality. Although oxidative stress is involved in the onset and progression of this disorder, the specific role of some main redox regulators such as catalase, the main scavenger of H2O2, remains unclear. In the present study, epigastric arteries of kidney transplant recipients, an in vivo model of VC and an in vitro model of VC exhibiting catalase overexpression (Cts) were analyzed. Peri-calcification areas of human epigastric arteries have increased levels of catalase and cytoplasmic rather than nuclear RUNX2. In the in vivo model, advanced aortic VC concurs with lower levels of the H2O2 scavenger, glutathione peroxidase 3 compared to controls. In an early model of calcification using vascular smooth muscle cells (VSMCs), Cts VSMCs showed the expected increase in RUNX2 total levels. However, Cts VMSC also exhibited lower percentage of the nucleus stained for RUNX2 in response to calcifying media. At this early model of VC we did not observe dysregulation of mitochondrial redox state, an increase in general redox state was observed in the cytoplasm. These in vivo and in vitro results highlight the complex role of antioxidant enzymes as catalase in the process of VC by regulation of RUNX2 location.

There are presently more than 18 known aflatoxins (>18) most of which have been insufficiently studied for their incidence, health-risk, and mechanisms of toxicity to allow effective intervention and control means that would significantly and sustainably reduce their incidence and adverse effects on health and economy. Among these, aflatoxin B1 (AFB1) has by far been the most studied; and yet, many aspects of the range and mechanisms of the diseases it causes remain to be elucidated. Its mutagenicity, tumorigenicity, and carcinogenicity, which are the best known still suffer from many limitations regarding the relative contribution of the oxidative stress and the reactive epoxide derivative (Aflatoxin-exo 8,9-epoxide) in the induction of the diseases, as well as its metabolic and synthesis pathways. Additionally, despite the well-established additive effects for carcinogenicity between AFB1 and other risk factors, e.g., hepatitis viruses B and C, and the algal hepatotoxic microcystins, the mechanisms of this synergy remain unclear. This study reviews the most recent advances in the mechanisms of toxicity of aflatoxins and the adverse health effects that they cause in humans and animals.

Chronic pain is a serious health concern and potentially debilitating condition, leading to anxiety, depression, reduced productivity and functionality, and poor quality of life. This condition can be even more detrimental and incapacitating in the pediatric patient population. In low and middle income countries (LMICs), pain services are inadequate or unavailable, leaving most of the world's pediatric population with chronic pain untreated. Many of these children in LMICs are suffering without treatment, and often die in pain. Awareness and advocacy for this population must be prioritized. We reviewed the available literature on the chronic pediatric pain burden in LMICs, barriers to treatments, and current efforts to treat these patients.

Down Syndrome (DS) is a chromosomal disorder due to the presence of an additional chromosome 21 that causes intellectual deficit and physical anomalies and predisposes patients to develop infections throughout their lives. Pneumonias are more serious in patients with DS, requiring hospitalization, and represent an important cause of mortality in this population. Cytomegalovirus (CMV) causes widespread and serious infections in immunocompromised individuals, affecting the respiratory tract and, causing interstitial pneumonia, is associated with a high mortality rate. However, CMV-induced pneumonia is not reported in DS patients. The prevalence and severity of CMV respiratory infections in subjects with DS is unknown. This case describes a 50-year-old female patient suffering from DS who developed extensive bilateral pneumonia with severe respiratory failure which required hospitalization in intensive care, intubation and mechanical ventilation after approximately 10 days of empiric antibiotic and anitimycotic therapy for fever, cough and dyspnea. The patient was diagnosed with CMV pneumonia and recovered after treatment with Ganciclovir. To the best of our knowledge, this is the first reported case of CMV pneumonia in a patient with DS. This case aims to highlight that CMV pneumonia in individuals with DS can be a life-threatening condition. It also clarifies the importance of early diagnosis of infections from opportunistic pathogens such as CMV to ensure timely and efficient treatment.

Symptoms attributed to the gastrointestinal manifestations of multi-system disorders play an important role in the long-term management of these conditions. Gastrointestinal complications of a variety of connective tissue disorders have been studied and there is an increased interest in the incidence and prevalence of these symptoms. Descriptions of the occurrence of gastrointestinal complications in Marfan syndrome have appeared infrequently in the medical literature. In this review article we focus on both structural and functional gastrointestinal pathology that may occur in patients with Marfan syndrome.

This study investigates the effects of ambient illumination and negatively polarized text color on visual fatigue, exploring the issue of visual fatigue when using visual display terminals in low-illumination environments. The research methodology utilized an experimental design to collect data on changes in pupil accommodation and blink rate through an eye tracker. Partici-pants completed a reading task while exposed to various text colors and ambient light conditions to evaluate visual fatigue and cognitive performance. The study's findings suggest that text color significantly affects visual fatigue, with red text causing the highest level of visual fatigue and yellow text causing the lowest level of visual fatigue. Improvements in ambient lighting reduce visual fatigue, but the degree of improvement varies depending on the text color. Additionally, cognitive performance is better when using yellow and white text but worse when using red text. Yellow text is the most effective choice for reducing visual fatigue under negative polarity. In-creasing ambient lighting can also improve visual fatigue in low-illumination conditions. These findings will offer valuable guidance for designing visual terminal device interfaces, especially for low-illumination or night environments, to minimize visual fatigue and improve the user ex-perience.

Thermoplastic composites are continuously replacing thermosetting composites in lightweight structures. However, the accomplished work on the fatigue behavior of thermoplastics is quite limited. In the present work, we propose a numerical modeling approach for simulating fatigue delamination growth and predicting the residual tensile strength of quasi-isotropic TC 1225 LM PAEK thermoplastic coupons. The approach is supported and validated by tension and fatigue (non-interrupted and interrupted) tests. Fatigue delamination growth is simulated using a mixed-mode fatigue crack growth model, which is based on the cohesive zone modeling method. All interfaces between the thermoplastic plies were modelled using cohesive elements. Quasi-static tension analyses on pristine and fatigued coupons were performed using a progressive damage model implementing a set of Hashin-type strain-based failure criteria and a damage mechanics-based material property degradation module. Using the fatigue model, delamination growth was predicted as a function of number of cycles at all interfaces. The results agree well with C-scan images taken on fatigued coupons during interruptions of fatigue tests. An unequal and unsymmetric delamination growth was predicted due to the quasi-isotropic lay-up. Moreover, the combined models capture the decrease in the residual tensile strength of the coupons. In the quasi-static tension analysis of the fatigued coupons, the driving failure mechanisms are the fast propagation of the pre-existing delamination and the severe matrix cracking.

This paper discusses the theoretical and experimental correlations between fatigue and static strength statistical distributions. We use a two-parameter residual strength model that obeys the qualitative Strenght-Life Equal-Rank (SLERA) assumption for guidance. The modeling approach consists of recovering the model's parameters by best fitting the constant amplitude (CA) fatigue data at a given stress ratio, R, and the experimental Weibull parameters of the static strength distribution function. Once the model's parameters are fixed, its capabilities, potential, and limits are discussed by comparing its predictions with residual strength and fatigue data obtained at different stress ratios, R. Moreover, from a preliminary analysis, the theoretical extension of the model's capabilities to variable amplitude loadings is conceptualized. The application of Miner's rule is also discussed and compared with a new damage rule to analyze the fatigue responses under variable amplitude loadings.

This article presents a method that uses a semi-automatic algorithm for the detection and analysis of microcracks in steel test specimens using binarized image analysis. It obtains the length along the crack path in contrast to previous methods that have obtained linear length, thereby achieving a closer approximation to its actual value. Additionally, this method automatically calculates the COD and COA parameters with measurement deviations in micrometres, thus providing greater precision than previous methods proposed to date.

A model to rationalize the effects of test temperature and microstructural variables on the creep crack growth (CCG) and creep-fatigue crack growth (CFCG) rates in ferritic steels is described. The model predicts that as the average spacing between grain boundary particles that initiate creep cavities decrease, the CCG and CFCG rates increase. Further, CCG data at several temperatures collapse into a single trend when a temperature compensated CCG rate derived from the model is used. CCG and CFCG behavior measured at different temperatures is used to assess the effects of variables such as differences between basemetal (BM), weldmetal (WM) and the heat-affected zone (HAZ) regions. The model is demonstrated for Grade 22 and Grade 91 steels using data from literature. It is shown that differences between the CCG behavior of Grade 22 steel in new and ex-service conditions are negligible in the BM and WM regions but not in the HAZ region. The CCG behavior of Grade 91 steels can be separated into creep-ductile and creep-brittle regions. The creep-brittle tendency is linked to the presence of excess trace element concentrations in the material chemistry. Significant differences found in the CCG rates between BM and the WM and HAZ regions of Grade 91 steel were explained.

The formation and propagation of cracks occurs through irreversible dislocation movements at notches, material defects and grain boundaries. Since this process is partly thermally controlled, the resistance to dislocation movements at low temperatures increases. This slows both fatigue initiation and fatigue crack propagation. From recent experimental data, it can be seen that fatigue crack growth is accelerated below the fatigue transition temperature (FTT) that correlates with the ductile-brittle transition temperature (DBTT) found by well-known fracture mechanics tests, i.e., Charpy impact, fracture toughness, and CTOD. Hence, this study investigates the relation between FTT and DBTT in S500 high-strength steel base material and welded joints at low temperatures using fatigue crack growth, fracture toughness tests as well as scanning electron microscopy. From the tests, an almost constant decrease in fatigue crack propagation rate is determined with decreasing test temperature even below the DBTT.

Fatigue loading is critical to fibre reinforced polymer composites due to their anisotropic and heterogenous nature. This study investigated the tensile fatigue behaviour of polyester and vinyl ester based GFRP laminates to understand the critical aspects of failure mode and fatigue life under cyclic loading. GFRP laminates with two different resin systems (polyester and vinyl ester), two different stress ratios (0.1 and 0.5) and two different environmental conditions (air and water) were investigated at an applied stress of 80%, 60% and 40% of the ultimate capacity. Based on the investigated parameters (i.e., resin types, stress ratio, environmental conditioning and maximum applied stress), a fatigue model was proposed. Results show that the resin system plays a great role in fatigue failure mode while the stress ratio and environmental condition significantly affect the tensile fatigue life of GFRP laminates. The types of resin used in GFRP laminates and environmental conditions as input parameter in the proposed fatigue model is a unique contribution.

We asked whether the level of peripheral fatigue would differ when three consecutive exercise trials were completed to task failure, and whether there would be delayed recovery in maximal voluntary contraction (MVC) force, neuromuscular activation and peripheral fatigue following task failure. Ten trained sport students performed three consecutive knee extension isometric trials (T1, T2, T3) to task failure without breaks between trials. T1 and T2 consisted of repeated 5-s contractions followed by 5-s rest. In T1, contractions were performed at a target force at 60% pre-exercise MVC. In T2, all contractions were MVCs, and task failure occurred at 50% MVC. T3 was a sustained MVC performed until force fell below 15% MVC. Evoked force responses to supramaximal electrical femoral nerve stimulation were recorded to assess peripheral fatigue. Electromyography signals were normalized to M-wave amplitude to assess neuromuscular activation. Lower levels of evoked peak forces were observed at T3 compared to T2 and T1. Within 5 s of task failure in T3, MVC force and neuromuscular activation recovered substantially without any recovery in evoked peak force. Neuromuscular activation 5-10 s after T3 was unchanged from pre-exercise values, but evoked peak forces were substantially reduced. These results challenge the existence of a critical peripheral fatigue threshold that reduces neuromuscular activation. Since neuromuscular activation changed independently of any change in evoked peak force, immediate recovery in force production after exercise is due to increased central recruitment and not to peripheral mechanisms.

Multiple sclerosis (MS) is a demyelinating autoimmune disorder of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) has been widely used to determine the pathogenesis of the disease and evaluate new treatment strategies for MS. Therefore, we investigated the efficacy of oral administration of a Myelin Oligodendrocyte Glycoprotein (MOG) in the treatment of EAE. Female C57BL/6 mice were utilized in three groups (Control group: received PBS orally; prevention group: oral administration of MOG35-55 two weeks before EAE induction; treatment group: oral administration of MOG35-55 after EAE induction. MOG administration, both as prevention and treatment, significantly controlled clinical score, weight loss, CNS inflammation, and demyelination, mainly through the modulation of T cell proliferation, reduction of pro-inflammatory cytokines and transcription factors, including TNF-α, IFN-γ, IL-17, T-bet, and ROR-γt. MOG administration, both as prevention and treatment, also induced anti-inflammatory cytokines and transcription factors, including IL-4, TGF-β, GATA-3, and Foxp3. The results showed that oral administration of MOG, both as prevention and treatment, could efficiently control EAE development. Immunomodulatory mechanisms include the induction of Th2 and Treg cells and the suppression of pro-inflammatory Th1 and Th17 cells.

Multiple sclerosis (MS) is a demyelinating autoimmune disorder of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) has been widely used to determine the pathogenesis of the disease and evaluate new treatment strategies for MS. Therefore, we investigated the efficacy of oral administration of a Myelin Oligodendrocyte Glycoprotein (MOG) in the treatment of EAE. Female C57BL/6 mice were utilized in three groups (Control group: received PBS orally; prevention group: oral administration of MOG35-55 two weeks before EAE induction; treatment group: oral administration of MOG35-55 after EAE induction. MOG administration, both as prevention and treatment, significantly controlled clinical score, weight loss, CNS inflammation, and demyelination, mainly through the modulation of T cell proliferation, reduction of pro-inflammatory cytokines and transcription factors, including TNF-α, IFN-γ, IL-17, T-bet, and ROR-γt. MOG administration, both as prevention and treatment, also induced anti-inflammatory cytokines and transcription factors, including IL-4, TGF-β, GATA-3, and Foxp3. The results showed that oral administration of MOG, both as prevention and treatment, could efficiently control EAE development. Immunomodulatory mechanisms include the induction of Th2 and Treg cells and the suppression of pro-inflammatory Th1 and Th17 cells.

The most frequent cause of cardiac failure globally is ischemic heart disease, with chemothera-py-related cardiovascular side effects emerging as the second most frequent cause. Cancer therapy can result in acute cardiac events, such as coronary artery spasm, acute myocardial infarction, thromboembolism, myocarditis, bradycardia, tachyarrhythmias, atrio-ventricular blocks, QT pro-longation, torsades de pointes, pericardial effusion and hypotension, as well as chronic conditions, such as hypertension, systolic and diastolic left ventricular dysfunction presenting clinically as heart failure or cardiomyopathy. In cardio-oncology, when referring to cardiac toxicity and cardiovas-cular hypersensitivity, there is a great deal of misunderstanding. When a dose-related cardiovas-cular side effect continues even after the causative medication is stopped, it is referred to as cardi-otoxicity. A fibrotic response is the ultimate outcome of cardiac toxicity, which is defined as a dose-related cardiovascular adverse impact that lasts even after the causative treatment is stopped. Cardiotoxicity can occur after a single or brief exposure. On the other hand, the term cardiac or cardiovascular hypersensitivity describes an inflammatory reaction that is not dose-dependent, can occur at any point during therapy, even with very low medication dosages, and can show up as Kounis syndrome. It may also be accompanied by anti-drug antibodies and tryptase levels. In this comprehensive review, we present the current views on cardiac toxicity and cardiovascular hypersensitivity, together with the reviewed cardiac literature on the chemotherapeutic agents inducing hypersensitivity reactions. Cardiac hypersensitivity seems to be the pathophysiologic basis of coronary artery spasm, acute coronary syndromes such as Kounis syndrome and myocardi-tis caused by cancer therapy.

Throughout this paper the effects of injuries on athletes are highlighted in different aspects. Exertional compartment syndrome is a specific injury related to athletes that is thoroughly explored in this paper through an analysis of the anatomy, symptoms, diagnosis and treatments of the syndrome. Exertional compartment syndrome is an exercise-induced muscle and nerve condition that causes pain, swelling as well as disability in the affected muscles of the lower leg. This syndrome commonly develops in young athletes involved in sports with excessive running and repetitive impact such as track and field, soccer, basketball and lacrosse. Exertional compartment syndrome is commonly misdiagnosed as other less severe injuries such as shin splints, which is symptomatic of pain along the tibia bone of the lower leg caused by overuse. The misdiagnosis of exertional compartment syndrome allows the syndrome to worsen and intensify resulting in the only effective treatment to be fasciotomy, a surgical procedure to release the pressure within the compartment of the lower leg. There is no definitive protocol developed for patients after fasciotomy is performed. Athletes experiencing similar symptoms after surgery are usually treated for their symptoms rather than the syndrome as a whole, which does not have a high degree of success. The development of a definitive protocol utilizing the techniques of manual therapy, mobility stretching and corrective strength training can improve the adverse effects of exertional compartment syndrome as well as restore functionality to the athlete. Raising awareness of this syndrome in athletics will be effective in treating the athlete early on in order to avoid severe effects and invasive procedures.

Both Stevens Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are main injurious cutaneous medication reactions that mostly affect the epidermis and mucus membranes. TEN and SJS affecting nearly 1 or 2/1,000,000 people per year, and can recognized as medical crises since they may be deadly. Mucocutaneous discomfort, hemorrhagic erosions, erythema, and more or less severe epidermal separation that appear as ulcer and patches of dermic loss are their defining characteristics. The sole difference between TEN and SJS at this time is the degree of skin detachment, making them two extremes of a spectrum of severe cutaneous adverse drug reactions (cADRs). In the majority of cases, drugs are considered as the principal reason of SJS/TEN, but herpes simplex virus and Mycoplasma pneumoniae infections are also recognized causes, along with lesser number of cases in which the cause is still unknown. Among the drugs with a "high" likelihood of producing TEN/SJS are carbamazepine (CBZ), trimethoprim-sulfamethoxazole, phenytoin, aminopenicillins, allopurinol, cephalosporins, other sulfonamide antibiotics, quinolones, phenobarbital, and NSAIDs of the oxicam variety. There is strong genetic evidence for SJS and TEN in Han Chinese due to the substantial association between the human leukocyte antigen (HLA-B*1502) and SJS brought on by CBZ. The diagnosis is made mostly based on clinical symptoms and the histological study of a dermal biopsy. Pemphigus vulgaris, bullous pemphigoid, linear IgA dermatosis, paraneoplastic pemphigus, disseminated fixed bullous drug eruption, acute generalized exanthematous pustulosis (AGEP), and staphylococcal scalded skin syndrome (SSSS) are among the differential diagnoses. The management of patients with SJS/TEN is complicated by the high risk of mortality, necessitating early diagnosis, estimation of the SCORTEN prognosis, identification and discontinuation of the causative drug, specialized supportive care, and high-dose injectable Ig therapeutic interventions. The reported fatality rates for SJS are 1-5% on average and 25-35% for TEN; it can be even higher in patients who are elderly or who have a significant amount of epidermal detachment on their skin. More than 50% of TEN patients who survive the disease experience long-term consequences.

SGLT2 inhibitors act to induce glucosuria and have been shown to be efficacious in the treatment of type II diabetes mellitus but have also been shown to positively affect cardiovascular conditions and some benefitting kidney function. SGLT2i have shown to be effective in more advanced conditions but may eventually be a treatment in more general metabolic dysfunction. Metabolic syndrome is a clinical diagnosis for establishing risk for ischemic heart disease and diabetes. The prevalence of type II diabetes mellitus, heart disease, and severe vascular events steadily increased over recent decades. In addition to the established benefits of diet and exercise, SGLT2 inhibitor therapy may be able to aid in the treatment of metabolic syndrome from its proven cardiovascular and anti-hyperglycemic benefits. Pharmacologic modeling in canines is also considered, as they present with similar diagnoses and offer a model that shares many of the characteristics of humans in metabolic dysfunction.

This observational study was ordered by the Medical Practitioners’ Chamber in Warsaw. The objective of the study was to evaluate the health status of physicians in relation to their occupational duties. Professional burnout was considered relative to different features of personality. This study was initially carried out from 2005–2008, but further analysis of burnout and personality was carried out from 2017–2018. The research tools were anonymous, validated questionnaires. The sample size was based on the size of the population— the registry of the Regional Chamber of Medical Practitioners— and literature on burnout prevalence. The respondents’ work places were randomly selected from the Mazovian District register. The test on burnout was completed by 378 respondents, while 62 subjects completed a personality test. Results showed that burnout syndrome was an occupational problem for healthcare workers. Professional burnout affected as many as 42% of respondents(n = 158). It affected two age groups in particular: physicians up to 31 years old and individuals aged 41-50. Moreover, neuroticism was found to be significantly related to burnout syndrome. In conclusion, burnout syndrome is common among medical practitioners, and neuroticism may be correlated with burnout syndrome.

Meier–Gorlin syndrome (MGS) is a rare genetic developmental disorder that causes primordial proportional dwarfism, microtia, absent or hypoplastic patellae and other skeletal anomalies. Overlapping skeletal symptoms make MGS difficult to diagnose clinically. We describe a 3-year-old boy with short stature, recurrent respiratory infections, short-rib dysplasia, tower head and facial dysmorphisms who was admitted to the Tomsk Genetic Clinic to verify a clinical diagnosis of Jeune syndrome. Clinical Exome sequencing revealed two variants (compound heterozygosity) in the ORC6 gene: c.2T&gt;C(p.Met1Thr) and c.449+5G&gt;A. In silico analysis showed the pathogenicity of these two mutations and predicted a decrease in donor splicing site strength for c.449+5G&gt;A. An in vitro minigene assay demonstrated that variant c.449+5G&gt;A causes a complete skipping of exon 4 in ORC6 gene. The parents asked for urgent prenatal testing for MGS for the next pregnancy, but it ended in a miscarriage. Thus, this case report may help to prevent MGS misdiagnosis in the future. We also performed in silico and functional analyses of ORC6 mutations and developed a restriction fragment length polymorphism and haplotype-based short-tandem-repeat assay for prenatal genetic testing for MGS. These findings should elucidate MGS aetiology and improve the quality of genetic counselling for affected families.

This study investigated the mechanical properties and fatigue behavior of FH36 steel plate rolled in different directions. By adopting a sequential rolling process in the rolling direction (RD) and transverse direction (TD), the differences in properties between RD and TD were eliminated, resulting in nearly identical tensile properties. The steel plate exhibited a yield strength of approximately 420 MPa, a tensile strength of approximately 506 MPa, and an elongation of approximately 25%. Fatigue tests conducted at room temperature and -60℃ showed a fatigue limit of the maximum stress of 488 MPa at room temperature and 500 MPa at -60℃, indicating improved low-temperature fatigue performance. The fracture surfaces displayed distinct characteristics, such as oblique shearing fractures for high-cycle fatigue and cup-cone shape fractures for low-cycle fatigue. The fatigue source zone were both on the surface of the specimens. As the maximum stress increased, the area of the crack propagation zone for high-cycle fatigue decreased, while the area of the final fracture zone, the number of dimples and the proportion of the LAGBs increased.

Myalgic Encephalomyelitis, also known as Chronic Fatigue Syndrome (ME/CFS) and Long COVID are characterized by debilitating post-exertional malaise and other core symptoms related to immune dysregulation resultant from post-viral infection, including mitochondrial dysfunction, chronic neuroinflammation and gut dysbiosis. The reported associations between altered microbiota composition and cardinal symptoms of ME/CFS and Long COVID, suggesting that use of microbial preparations, such as probiotics, by restoring the homeostasis of the brain-immune-gut axis may help in the management of symptoms in both conditions. Therefore, this review aims to investigate the implications of alerted gut microbiome and assess the evidence supporting use of microbial-based preparations, including probiotics, synbiotics, postbiotics alone and/or in combination with other nutraceuticals in the management of fatigue, inflammation, as well as neuropsychiatric and gastrointestinal symptoms among patients with ME/CFS and Long COVID.

Considering the relevance of the pathogenesis research of different liver diseases, in our study we investigated the possible activity of IL-23/IL-17 axis on the im-munohepatotoxicity of two etiologically different CLD. A total of patients with CHC infection, 19 with NASH and 20 healthy controls (CG) were recruited. After histological verification from liver tissue obtain by liver biopsy, patients with CHC were divided into two groups: CHC-NSF (F0/F1/F2)-non-significant fibrosis, 20 patients, and CHC-SF (F3/F4)-significant fibrosis/cirrhosis, 16 patients. All anthropometric, biochemical, immunological cytokines (IL-6, IL-10, IL-17 and IL-23) tests were performed accordance to standard procedure. The plasma levels of IL-6, Il-17A and IL-23 were significantly higher in CHC-SF and NASH in compared with CG. Also, plasma levels of IL-23/IL-17A were significantly higher in NASH in compared to CHC-SF. In CHC-SF we had significantly lowest IL-10 level in compared with all three groups. Liver tissue levels of IL-17A and IL-23 in CHC-NSF were significantly lower in compared with NASH. IN CHC-SF and NASH, IL17-A and IL-23 in liver tissue were significantly higher in compare to plasma levels. In conclusan, proinflammatory response of IL-23/17A axis is dominant in plasma and liver tissue in CHC with higher levels of liver fibrosis and in NASH patients.

Interior permanent magnet motors (IPMSMs) are extensively used as traction motors today because of their exceptional torque and power density, and wide constant power operating range. Under real-world usage, an IPMSM rotor undergoes varying electromagnetic, thermal, and mechanical loads. Under such conditions, fatigue life-based design criteria should be utilized over stress-based design criteria to ensure the structural integrity of the rotor. Moreover, the driving dynamics can change the rotor temperature continuously, which affects the electromagnetic, mechanical, and fatigue properties of rotor material. This paper proposes a robust thermo-mechanical rotor fatigue simulation workflow considering the significant loads acting on an IPMSM rotor and the temperature variation throughout a drive cycle. It discusses an accelerated fatigue life estimation approach based on peak valley extraction to reduce the simulation time significantly for stress and fatigue analysis. Then, it presents a method for stress-life curve generation for a variable loading. It also presents a sensitivity study with a median S-N curve, and a 90%-reliability 95%-confidence (R90C95) S-N curve.

Most of the damage to Vleg cars was caused by material fatigue. The objectives of the fatigue analysis on Xenia 2011 car wheels with the Finite Element Method using Solidworks are: 1) Knowing the fatigue analysis process on car wheels, 2) Knowing the results of the fatigue analysis on car wheels. The research method used is the Finite Element Method (FEM) method; the re-search steps include model data retrieval from the Wheel code, 3D model creation process, static simulation process according to SAE J 328 standard, mesh variations, fatigue simulation, and finally, standardization of results fatigue simulation regarding the SAE J 328 standard. The re-sults of the fatigue analysis on the Xenia 2011 car wheels obtained an age of 1000,000 cycles when compared with the minimum average of SAE J 328 of 600,000 cycles, this product design is clas-sified as a high cycle, which means it will experience a prolonged failure, and this design has a maximum alternating stress value of 627.4702 MPa, a strain of 0.007105, a displacement of 7.148 mm and a SOF of 0.087890 with a load factor used of 2.5, so overall this Xenia car can be loaded with a load of 1775 kg, if it is more than that, then Wheels will experience cracking.

Most of the research of mental fatigue evaluation mainly concentrated on some indexes that require sophisticate and large instruments which make the detection of mental fatigue cumbersome, time-consuming, and difficult to apply on a large scale. A quick and sensitive mental fatigue detection index is necessary so that mental workers can be alerted in time and take corresponding countermeasures. But to date, no studies have compared the sensitivity of common objective evaluation indexes. To solve these problems this study recruited 56 human subjects. These subjects were evaluated using six fatigue indexes: the Stanford sleepiness scale, digital span, digital decoding, short-term memory, critical flicker fusion frequency (CFF), and speed perception deviation. The results of fatigue tests before and after mental fatigue were compared, and a one-way analysis of variance (ANOVA) was performed on the speed perception deviation. The result indicated the significance of this index. Considering individual differences, the relative fatigue index (RFI) was proposed to compare the sensitivity of the indexes. The results showed that when the self-rated fatigue grade changed from non-fatigue to mild fatigue, the ranges of RFI values for digital span, digital decoding, short-term memory and CFF were 0.175–0.258, 0.194–0.316, 0.068–0.139, and 0.055–0.075, respectively. Correspondingly, when the self-rated fatigue grade changed from non-fatigue to severe fatigue, the ranges of RFI values for the above indexes were 0.175–0.258, 0.194–0.316, 0.068–0.139, and 0.055–0.075, respectively. These results suggest that the sensitivity of the digital decoding, digital span, short-term memory, and CFF decreased sequentially when the self-evaluated fatigue grade changed from no fatigue to mild or severe fatigue. The RFI individuality of the speed perception deviation is highly variable and is not suitable as an evaluation index. In mental fatigue testing, digital decoding testing can provide faster, more convenient, and more accurate results.

Medium-carbon steel is commonly used for the rail, wire ropes, tire cord, cold heading, forging steels, cold finished steel bars, machinable steel and so on. Its fatigue behavior analysis and fatigue life estimation play an important role in the machinery industry. In this paper, the estimation of fatigue life of medium-carbon steel with different surface roughness using established S-N and P-S-N curves is presented. To estimate the fatigue life, the effect of the average surface roughness on the fatigue life of medium-carbon steel has been investigated using 75 fatigue tests in three groups with average surface roughness (Ra): 0.4μm, 0.8μm, and 1.6μm respectively. S-N curves and P-S-N curves have been established based on the fatigue tests. The fatigue life of medium-carbon steel is then estimated based on Tanaka-Mura crack initiation life model, the crack propagation life model using Paris law, and material constants of the S-N curves. 6 more fatigue tests have been conducted to validate the presented fatigue life estimation formulation. The experimental results have shown that the presented model could estimate well the mean fatigue life of medium-carbon steel with different surface roughness

Malassezia are lipid-dependent basidiomycetous yeast of the normal skin microbiome, although Malassezia DNA has been recently detected in other body sites and has been associated with cer-tain chronic human diseases. This new perspective raises many questions. Are these yeasts truly present in the investigated body site or were they contaminated by other body sites, adjacent or not? Does this DNA contamination come from living or dead yeast? If these yeasts are alive, do they belong to the resident mycobiota or are they transient colonizers which are not permanently established within these niches? And, finally, are these yeasts associated with certain chronic diseases or not? In an attempt to shed light on this knowledge gap, we critically re-viewed the 31 published studies focusing on the association of Malassezia spp. with chronic human diseases, including psoriasis, atopic dermatitis (AD), chronic rhinosinusitis (CRS), asthma, cystic fibrosis (CF), HIV infection, inflammatory bowel disease (IBD), colorectal cancer (CRC), and neurodegenerative diseases.

This study investigates the power production and blade fatigue of a three-turbine array subjected to active yaw control (AYC) in full-wake and partial-wake configurations. A framework of two-way coupled large-eddy simulation (LES) and aeroelastic blade simulation is applied to simulate the atmospheric boundary-layer (ABL) flow through the turbine array and the structural responses of the turbine blades. Mean power outputs and blade fatigue loads are extracted from the simulation results. By exploring the feasible AYC decision space, we find that (a) in the full-wake configuration, the local power-optimal AYC strategy with positive yaw angles endures less flapwise blade fatigue and more edgewise blade fatigue than the global power-optimal strategy; (b) in the partial-wake configuration, applying positive AYC in certain inflow wind directions achieves higher optimal power gains than that in the full-wake scenario and reduces the blade fatigue from the non-yawed benchmark. Through a theoretical analysis based on the blade element momentum theory, we reveal that the aforementioned differences in flapwise blade fatigue between the positively and negatively yawed turbine are due to the differences in the azimuthal distributions of the local relative velocity on blade sections, resulting from the combined effects of vertical wind shear and blade rotation. Furthermore, the difference in the blade force between the positively and negatively yawed front-row turbine induces different wake velocity and turbulence distributions, causing different fatigue loads on the downwind turbine exposed to the wake.

The fatigue life of concrete is affected by many interwoven factors whose effect is nonlinear. Be-cause of its unique self-learning ability and strong generalization capability, the Bayesian regu-larized backpropagation neural network (BR-BPNN) is proposed to predict concrete behavior in tensile fatigue. The optimal model was determined through various combinations of network parameters. The average relative impact value (ARIV) was constructed to evaluate the correla-tion between fatigue life and its influencing parameters (maximum stress level Smax, stress ratio R, static strength f, failure probability P). ARIV results were also compared with other factor as-sessment methods (weight equation and multiple linear regression analyses). Using BR-BPNN, S-N curves were then obtained for the combinations of R=0.1, 0.2, 0.5; f=5, 6, 7MPa; P=5%, 50%, 95%. The tensile fatigue results under different testing conditions were finally compared for compatibility. It was concluded that Smax has the most significant negative effect on fatigue life; the degree of influence of R, P, and f, which positively correlate with fatigue life, decreases suc-cessively. ARIV is confirmed as a feasible way to analyze the importance of parameters and could be recommended for future applications. The tensile fatigue performance of plain concrete under different stress states (flexural tension, axial tension, splitting tension) does not differ sig-nificantly. Besides utilizing the valuable fatigue test data scattered in the literature, insights gained from this work could provide a reference for subsequent fatigue test program design and fatigue evaluation.

Aim: To determine whether an AI model and single sensor measuring acceleration and ECG could model cognitive and physical fatigue for a self-paced trail run. Methods: A field-based protocol of continuous fatigue repeated hourly induced physical (~45 minutes) and cognitive (~10 minutes) fatigue on one healthy participant. Physical load was a 3.8 km, 200 m vertical gain, trail run with acceleration and electrocardiogram (ECG) data collected using a single sensor. Cognitive load was a Multi Attribute Test Battery (MATB) and separate assessment battery including the Finger Tap Test (FTT), Stroop, Trail Making A and B, Spatial Memory, Paced Visual Serial Addition Test (PVSAT), and a vertical jump. A fatigue prediction model was implemented using a Convolutional Neural Network (CNN). Results: When the fatigue test battery results were compared for sensitivity to the protocol load, FTT right hand (R2 0.71) and Jump Height (R2 0.78) were the most sensitive while the other tests were less sensitive (R2 values Stroop 0.49, Trail Making A 0.29, Trail Making B 0.05, PVSAT 0.03, spatial memory 0.003). Best prediction results were achieved with a rolling average of 200 predictions (102.4 s), during set activity types, mean absolute error for ‘walk up’ (MAE200 12.5%) and range of absolute error for ‘run down‘ (RAE200 16.7%). Conclusion: We were able to measure cognitive and physical fatigue using a single wearable sensor during a practical field protocol including contextual factors in conjunction with a neural network model. This research has practical application to fatigue research in the field.

The application of instrumented indentation to assess material properties like Young’s modulus and micro-hardness has become a standard method. In recent developments, indentation experiments and simulations have been combined to inverse methods, from which further material parameters as yield strength, work hardening rate, and tensile strength can be determined. In this work, an inverse method is introduced by which material parameters for cyclic plasticity, i.e. kinematic hardening parameters, can be determined. To accomplish this, cyclic Vickers indentation experiments are combined with finite element simulations of the indentation with unknown material properties, which are then determined by inverse analysis. To validate the proposed method, these parameters are subsequently applied to predict the uniaxial stress-strain response of a material with success. The method has been validated successfully for a quenched and tempered martensitic steel and for technically pure copper, where an excellent agreement between measured and predicted cyclic stress-strain-curves has been achieved. Hence, the proposed inverse method based on cyclic nanoindentation, as a quasi-non-destructive method, could complement or even substitute the resource-intensive conventional fatigue testing in the future for some applications.

This paper aims to analyse the mechanical properties response of polylactic acid (PLA) parts manufactured through fused filament fabrication. The influence of six manufacturing factors (layer height, filament width, fill density, layer orientation, printing velocity, and infill pattern) on the flexural resistance of PLA specimens is studied through an L27 Taguchi experimental array. Different geometries have been tested on a four-point bending machine and on a rotating bending machine. From the first experimental phase, an optimal set of parameters deriving in the highest flexural resistance have been determined. Results show that layer orientation is the most influential parameter, followed by layer height, filament width, and printing velocity, whereas the fill density and infill pattern show no significant influence. Finally, the fatigue fracture behaviour is evaluated and compared with previous studies results, to present a comprehensive study of the mechanical properties of the material under different kind of solicitations.

Chitinase 3-like 1 （also known as CHI3L1 or YKL-40）is a mammalian chitinase that has no enzymatic activity, but has the ability to bind to chitin, the polymer of N-acetylglucosamine (GlcNAc). Chitin is a component of fungi, crustaceans, arthropods including insects and mites, and parasites, but is completely absent from mammals, including humans and mice. In general, chitin-containing organisms produce CHI3L1 to protect the body from exogenous pathogen as well as hostile environments, and it was thought that it has a similar effect in mammals. However, recent studies have revealed that CHI3L1 plays a pro-inflammatory role by inducing anti-apoptotic activity in epithelial cells and macrophages. Under chronic inflammatory conditions such as inflammatory bowel disease and chronic obstructive pulmonary disease, many groups already confirmed that the expression of CHI3L1 is significantly induced on the apical side of epithelial cells, and activates many downstream pathways involved in inflammation and carcinogenesis. In this review article, we will summarize the expression of CHI3L1 under the chronic inflammatory conditions in various disorders and would like to discuss the potential roles of CHI3L1 in those disorders on various cell types.

Fragile X syndrome (FXS) is the most frequent monogenic form of autism spectrum disorder (ASD). Autistic FXS is caused by loss of the fmr1 gene product, the fragile X mental retardation protein (FMRP), triggering physiological and behavioral abnormalities. It is correlated with clock components for behavioral circadian rhythm. Mutation of this gene causes the disturbances in sleep patterns and circadian behavior commonly observed in patients with autistic FXS, accompanied by frequent dysregulation of melatonin synthesis and melatonin-dependent signaling. These changes impair vigilance, learning and memory, and are also linked to autistic behavior including the abnormal anxiety response. However, although several possible causes, symptoms, and clinical features of ASD have been investigated, the correlation between an altered circadian rhythm and autistic FXS has not been extensively studied. Recent works have highlighted the impact of melatonin on the nervous, immune, and metabolic systems. Even though utilization of melatonin for sleep disorder in ASD has been considered in clinical research, further studies should be aimed at its neuroprotective role in ASD during developmental period. In this review, we focus on the regulatory circuits involved in melatonin dysregulation and circadian system disruption in those with autistic FXS. Additionally, we discuss the neuroprotective effect of melatonin intervention. This may improve neuroplasticity and physical capability. We also review the underlying molecular mechanisms, and suggest that melatonin may be a useful novel treatment for autistic FXS, countering the adverse effects of circadian variation.

The ingestion of ethanol presents a significant global public health challenge. Chronic alcohol consumption is associated with the development of conditions such as cancer, cirrhosis, hepatic diseases, cardiovascular diseases, and diabetes, as well as neurological impairments that may predispose individuals to dementia, schizophrenia, and behavioral disorders such as violence and suicide. Alcohol-related fatalities constitute 5.3% of worldwide deaths annually, totaling approximately 3 million. Notably, alcohol consumption is implicated in 25% of cirrhosis-related deaths and 4.1% of cancer-related deaths. Taurine (2-aminoethanesulfonic acid) is a non-protein β-amino acid essential for cellular homeostasis, possessing antioxidant, anti-inflammatory, and cytoprotective properties crucial for life maintenance. This study aimed to evaluate the effects of taurine administration on hippocampal neurogenesis, neuronal preservation or reverse damage in rats exposed to forced ethanol consumption. Results demonstrated the neuroprotective effects of taurine on ethanol-treated rats, promoting tissue regeneration and suggesting its pivotal role in this process. However, this aminoacid failed to induce neurogenesis in the tissues of healthy rats, implying that its activity may be contingent upon post-injury stimuli.

In the world, migraine is one of the most common cause of disability in adults. To date, there is no a single cause for this disorder, but rather a set of physio-pathogenic triggers, in combination with a genetic predisposition. Among factors related to the migraine onset, a crucial role seems to be played by gut dysbiosis. In fact, it has been demonstrated how the intestine is able to modulate the central nervous system activities, through the gut-brain axis, and how gut dysbiosis can influence neurological pathologies, including migraine attacks. In this contest, in addition to migraine conventional pharmacological treatments, attention has been paid to an adjuvant therapeutic strategy based on different nutritional approaches and lifestyle changes able to positively modulate the gut microbiota composition. In fact, the restoration of the balance between the different gut bacterial species, the reconstruction of the gut barrier integrity and the control of the release of gut-derived inflammatory neuropeptides, obtained through specific nutritional patterns and lifestyle changes, represent a possible beneficial additive therapy for many migraine subtypes. Herein, this review explores the bi-directional correlation between migraine and the main chronic non-communicable diseases, like diabetes mellitus, arterial hypertension, obesity, cancer and chronic kidney diseases, whose link is represented by gut dysbiosis.

Cardiovascular diseases (CVD) account for about 17.3 million annual deaths worldwide. 85% of these deaths occurred as a result of myocardial infarction (MI) and stroke. Chronic heart diseases, such as arterial hypertension (AH), coronary heart disease, various cerebrovascular diseases, dilated and hypertrophic cardiomyopathies are widespread, with a fairly high incidence of mortality and disability. Most of these diseases are characterized by cardiac arrhythmias, conduction and contractility disorders. Additionally, interruption of the electrical activity of the heart, the appearance of extensive ectopic foci and heart failure are all symptoms of a number of severe hereditary diseases. The molecular mechanisms leading to the development of CVD are associated with impaired permeability and excitability of cell membranes and mainly caused by dysfunction of cardiac Ca2+ channels. Acquired channelopathies are caused by metabolic disorders, increased tone of the sympathetic nervous system, age-related changes that lead to deterioration of coronary blood flow and hemodynamics. Currently known channelopathies, such as the long or short QT syndromes, Brugada and Lenegre syndromes, catecholaminergic polymorphic ventricular tachycardia, etc., are congenital and genetic disorders caused by mutations of genes "responsible" for the conductive properties of certain channel-forming proteins, including pore-forming subunits of Ca2+ channels. Over the past 50 years, more than 100 varieties of ion channels have been found in the cardiovascular system cells. The relationship between the activity of these channels and cardiac pathology, as well as the general cellular biological function, has been intensively studied on several cell types and experimental animal models in vivo и in situ. In this review, we discuss the origin of Ca2+ channelopathies and the role of Ca2+ channels of various types: L- R-, T-types voltage-gated calcium channels, RyR2, non-selective hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, transient receptor potential (TRPC, TRPM7, TRPA1) channels in the development of cardio-vascular pathology.

Background: Overall survival is the most important outcome for treatment response in feline chronic kidney disease (CKD). Beraprost has been shown to reduce the kidney function decline in cats with International Renal Interest Society (IRIS) stage 2 and 3 CKD. However, association with prolonged survival has not yet been examined. Objective: To assess the relationship between beraprost and overall survival in cats with CKD in real clinical practice. Animals: Client-owned cats with IRIS stage 3 CKD (n = 134), evaluated between 2017 and 2020. Methods: Retrospective cohort study based on data from electronic medical records of one hospital. Results: Multivariable Cox regression models on all treatment effects showed that beraprost only was related to better survival (P = 0.028). The cohort was divided into “beraprost therapy” and “no beraprost therapy” groups, and survival analyses revealed that overall survival was significantly longer in the beraprost therapy group, using Kaplan-Meier curves (P = 0.004). However, baseline phosphate is known to be an important prognostic indicator and was not well balanced between the two groups. Therefore, a subcohort of 97 cats was selected (those having baseline phosphate < 6.0 mg/dL) that allowed for this parameter to be balanced between groups. The survival data in this subcohort was consistent with that of the overall study cohort. Conclusions: In feline patients with CKD, beraprost therapy was associated with better overall survival.

Stress plays a central role in functioning for all life forms. As humans, we experience stress in a multitude of ways through various types of stimuli. Due to the constancy of stressors in our lives, the nervous system has learned to allosterically adapt to the stimuli, but when the body cannot adapt, chronic stress can have morphological and degenerative impacts on neuroanatomy and cognitive function that may or may not be reversible. This literature review aimed to identify the specific neuroanatomical structures impacted most by the long-term effects of chronic stress and the subsequent relationship the morphological changes had on cognitive function in rodent models. We examined articles published from PubMed, Google Scholar, and Science Direct, while focusing the search on anatomical and neurodegenerative effects associated with chronic stress stimuli. The degenerative effects of various types simulated physiological chronic stress showed the most impact on neurogenesis and neuronal development, brain plasticity, and spatial learning and memory with association to the hippocampus. The hippocampus, amygdala, prefrontal cortex, and hypothalamic-pituitary-adrenal axis (HPA) all had reversible and non-reversible morphological alterations, which also had a direct impact on the brain’s cognitive abilities. While studies regarding chronic stress are still being conducted, future research may be able to further highlight why stressful stimuli can particularly impact these structures and the tangential impacts that it may have on related or adjacent structures.

Tinnitus is an auditory phantom perception in the ears or head in the absence of a corresponding external stimulus. There is currently no effective treatment available that reliably reduces tinnitus. Educative counseling is a treatment approach that aims to educate patients and inform them about possible coping strategies. For this feasability study, we implemented educational material and self-help advice in a smartphone app. Participants used the educational smartphone unsupervised during their daily routine over a period of 4 months. Comparing the tinnitus outcome measures before and after smartphone-guided treatment, we measured changes in the tinnitus-related distress, but not in tinnitus loudness. Improvements on the Tinnitus Severity numeric rating scale reached an effect size of .408, while the improvements on the THI were much smaller with an effect size of .168. Analysis on the user behavior showed that frequent and intensive use of the app is a crucial factor for treatment success: participants that used the app more often and interacted with the app intensively, reported a stronger improvement of the tinnitus. Between study allocation and final assessment, 26 of 52 participants dropped out of the study. Reasons for the dropouts and lessons for future studies are discussed in this paper.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm constituting approximately 15% of newly diagnosed leukemia in adult patients. Development of tyrosine kinase inhibitors (TKIs) have dramatically improved outcomes in patients with chronic CML in chronic phase. However, adverse drug events (ADEs) associated with TKI therapy have influenced drug adherence, resulting in adverse clinical outcomes and a decline in the quality of life (QoL). In this study, we carried out a unique questionnaire survey to evaluate ADEs, which comprised 14 adverse events. We compared drug adherence rates between patients using imatinib and those who switched from imatinib to nilotinib, a second-generation TKI. Following the switch, the total number of ADEs decreased considerably in most cases. Simultaneously, better QoL was observed in the nilotinib group than in the imatinib group. Drug adherence was measured using Morisky’s 9-item Medication Adherence Scale (MMAS). MMAS increased significantly after switching to nilotinib in all cases. Drug adherence is a critical factor for achieving molecular response in patients with CML. In fact, our results showed a strong inverse correlation between clinical outcome [international scale (IS)] and adherence (MMAS), with a stronger tendency in the nilotinib group than in the imatinib group. In conclusion, low occurrence of ADEs induced a high level of QoL and a good clinical response with second-generation TKI nilotinib treatment.

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

Treacher Collins syndrome (TCS) is a rare congenital disorder characterized by craniofacial abnormalities due to underdeveloped facial bones. In addition to physical deformities, TCS also presents with several neurological disorders resulting from facial defects and brain malformations. This paper reviews the neurological manifestations of TCS with a focus on facial nerve paralysis, neurodevelopmental delay, intellectual disability, and autism spectrum disorder. Facial nerve hypoplasia leads to an inability to control facial muscles and expressions. Neurodevelopmental delays in motor function and language acquisition are commonly reported in infants with TCS due to hearing loss, facial impairments, poor nutrition, infections, and structural brain changes. Intellectual disability with below average IQ is also more prevalent in TCS, affecting about one third of patients. Brain imaging reveals abnormalities like white matter hypoplasia, cortical atrophy, and reduced grey matter volume which likely contribute to cognitive deficits. Additionally, the rate of autism spectrum disorder is significantly higher in TCS compared to the general population. The reasons are unclear but may involve hearing loss, facial dysmorphisms, and socio-emotional processing centers in the brain. Management is multidisciplinary, focusing on early interventions like speech, physical, feeding, and behavioral therapy to maximize developmental and functional outcomes. Further research on the neurological pathophysiology of TCS is needed to better elucidate the mechanisms linking craniofacial defects with adverse neurodevelopmental consequences.

Prediction and early detection of atrial fibrillation (AF) remain a permanent challenge in everyday practice. Timely identification of an increased risk for AF episodes (which are frequently asymptomatic) is essential in the primary and secondary prevention of cardioembolic events. One of the noninvasive modalities of AF prediction is represented by the electrocardiographic P-wave analysis. This includes the study and diagnosis of interatrial conduction block (Bachmann`s bundle block). Bayés’ Syndrome (named after its first descriptor) denotes the association between interatrial conduction defect and supraventricular arrhythmias (mainly AF) predisposing to cardioembolic events. Our short review presents an update of the most important data concerning this syndrome: brief history, main ECG features, pathophysiological background and clinical implications.

Aims: Clinical evidence indicates that innate immune cells may contribute to the onset and outcome of acute coronary syndrome (ACS). Our prospective study aimed at analysing neutrophil phenotypes in ACS and their role in predicting 1-year major cardiovascular events. Methods: Blood neutrophil phenotypes were analysed by flow cytometry. Differential blood cell count and plasma levels of soluble markers were recorded at admission and at 6-month follow-up. Results: 108 patients categorized in chronic stable coronary artery disease (n=37), unstable angina (UA) (n=19), Non-ST-Elevation Myocardial Infarction (NSTEMI) (n=25), and ST-Elevation Myocardial Infarction (STEMI) (n=27) were included. STEMI and NSTEMI patients displayed higher neutrophil count and neutrophil-to-lymphocyte ratio (NLR) than stable and UA patients (P<0.0001), which normalized at 6-month after MI. STEMI patients were characterized by elevated percentages of band cells in low-density neutrophils (P=0.007) and in high-density neutrophils (P=0.019) compared to the other patients. Multivariable logistic regression analysis revealed that plasma levels of total MPO was associated with STEMI when compared to stable (OR: 1.434; 95% CI: 1.119-1.837; P<0.0001), UA (1.47; 1.146-1.886; P=0.002), and NSTEMI (1.213; 1.1-1.134; P=0.0001) patients, while increased neutrophil SSC signal intensity was associated with NSTEMI compared to stable patients (3.828; 1.033-14.184; P=0.045). Based on multivariable Cox regression analysis, elevated plasma levels of PCSK9 and low-density neutrophil percentage predicted 1-year outcome independently of cardiovascular risk factors (c-index: 0.915; IQR: 0.908-0.929). Conclusions: Changes in neutrophil phenotype are concomitant to ACS. These changes may differ between STEMI and NSTEMI. They may also contribute to ACS risk and patient outcome.

Loss-of-function mutations of the spermine synthase gene (SMS) result in Snyder-Robinson Syndrome (SRS), a recessive X-linked syndrome characterized by intellectual disability, osteoporosis, hypotonia, speech abnormalities, kyphoscoliosis, and seizures. As SMS catalyzes the biosynthesis of the polyamine spermine from its precursor spermidine, SMS deficiency causes a lack of spermine with an accumulation of spermidine. As polyamines, spermine and spermidine play essential cellular roles that require tight homeostatic control to ensure normal cell growth, differentiation, and survival. Using patient-derived lymphoblast cell lines, we sought to comprehensively investigate the effects of SMS deficiency on polyamine homeostatic mechanisms including polyamine biosynthetic and catabolic enzymes, derivatives of the natural polyamines, and polyamine transport activity. In addition to decreased spermine and increased spermidine in SRS cells, ornithine decarboxylase activity and its product putrescine were significantly decreased. Treatment of SRS cells with exogenous spermine revealed that polyamine transport was active, as the cells accumulated spermine, decreased their spermidine level, and established a spermidine-to-spermine ratio within the range of wild type cells. SRS cells also demonstrated elevated levels of tissue transglutaminase, a change associated with certain neurodegenerative diseases. These studies form a basis for further investigations into the leading biochemical changes and properties of SMS-mutant cells that potentially represent therapeutic targets for the treatment of Snyder-Robinson Syndrome.

Insulin resistance is a prominent pathophysiologic syndrome in a plethora of metabolic disorders including obesity, prediabetes, type 2 Diabetes Mellitus (Ten et al., 2007), impaired glucose tolerance, dyslipidemia, polycystic ovary syndrome and hypercoagulability (Smith & LeRoith, 2004). It is strongly associated with obstructive sleep apnea, hypoventilation syndrome, pancreatitis, nonalcoholic fatty liver disease, steatohepatitis, cirrhosis, gall bladder disease, multiple cancers (breasts, uterus, cervix prostate, kidney, colon, esophagus, pancreas and liver), stroke, cataracts, coronary heart disease, and hypertension. It is also associated with causation of abnormal menses, infertility, polycystic ovary syndrome, osteoarthritis, phlebitis and other venous diseases. Insulin resistance is thought to be caused by intrinsic and extrinsic factors that contribute to its development. Once present, insulin resistance affects the metabolism, behavior, physical appearance and has lasting effects. This paper will review the latest evidence in development of insulin resistance, its pathogenesis and manifestation and its relation to other conditions. The final aim is to raise awareness of its role on diet, metabolic, genetics and microbiome.

Due to the proliferation of genetic testing, pathogenic germline variants predisposing to hereditary hematological malignancy syndrome (HHMS) have been identified in an increasing number of genes. Consequently, the field of HHMS is gaining recognition among clinicians and scientists worldwide. Patients with germline genetic abnormalities often have poor outcomes and are candidates for allogeneic hematopoietic stem cell transplantation (HSCT). However, HSCT using blood from a related donor should be carefully considered because of the risk that the patient may inherit a pathogenic variant. At present, we now face the challenge of incorporating these advances into clinical practice for patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) and optimizing the management and surveillance of patients and asymptomatic carriers, with the limitation that evidence-based guidelines are often inadequate. The 2016 revision of the WHO classification added a new section on myeloid malignant neoplasms, including MDS and AML with germline predisposition. The main syndromes can be classified into three groups. Those without pre-existing disease or organ dysfunction; DDX41, TP53, CEBPA, those with pre-existing platelet disorders; ANKRD26, ETV6, RUNX1, and those with other organ dysfunctions; SAMD9/SAMD9L, GATA2, and inherited bone marrow failure syndromes. In this review, we will outline the role of the genes involved in HHMS in order to clarify our understanding of HHMS.

Introduction: Obstructive Sleep Apnea (OSA) is a respiratory condition identified by the partial or complete obstruction of the upper air passages during sleep. These episodes can lead to complications in neurobehavioral and cognitive domains and cardiovascular issues, especially in children. The involvement of OSA in ocular health during adulthood has been reported, but it remains a topic of debate in pediatric cases. Objective: This review aims to analyze the correlation between OSAS and ocular health in children. Specifically, it investigates the effects of OSA on ocular structures and conditions and explores potential improvements through treatment. Subjects and Methods: The research employed three search engines: PUBMED/MEDLINE, SCOPUS, and WebOfScience. After initial identification, 120 irrelevant articles were excluded. Of these, 10 pertained to the adult population, and 110 focused on the pediatric population. Following a careful selection process and the application of enrollment criteria, six relevant articles were included, all in English, focusing on the effects of OSA on children's eyes. Among these, three studies explored correlations with choroidal alterations, while three investigated retinal and optic nerve changes. Two studies analyzed post-otorhinolaryngological intervention ocular changes. Results: OSA leads to increased intraocular pressure and reduced optic nerve thickness in adults, but treatment alleviates this condition. An immediate correlation between OSA and optic nerve thickness in children does not readily emerge, although age appears to play a role. Pediatric patients with OSA exhibit corneal anomalies and an increase in optic nerve thickness, possibly due to intermittent hypoxia. Studies indicate that OSA can influence retinal vascular density in children, with an increase observed after treatment and reduced choroidal thickness in cases of adenotonsillar hypertrophy. Conclusion: This literature review has highlighted how OSA in children can significantly impact ocular health, with observed alterations in the optic nerve, choroid, retina, and cornea. While the direct correlation with the optic nerve may not always be evident, OSA can elevate intraocular pressure and lead to structural changes. However, treatment appears to bring about improvements. The necessity for regular monitoring to detect potential adverse effects underscores the importance of promptly addressing childhood OSA.

Abstract: Background and Objectives: A growing number of epidemiologic studies have found that diabetes mellitus may increase cancer risk and is implicated in numerous other metabolic and inflammatory disorders. The increase in pro-inflammatory cytokines plays a major role in insulin resistance and leads to hypoalbuminemia, and micro- and macrovascular diabetes complications, including kidney disease and anemia. This study aimed to investigate the utility of CEA, CRP, serum albumin level, hemoglobin, and LDH as biomarkers for cancer risk and the biological implications of diabetes on the evolution and prognosis of oncological patients. Material and methods: We conducted a retrospective, longitudinal, observational study, on a total group of 434 patients, 217 diagnosed with a form of cancer and with type 2 diabetes as a comorbidity, and the other 217 – control group, without diabetes. These patients were admitted to the oncology clinic. In subgroups, the same number of patients was considered, depending on the location of the oncological pathology. Anemia, hypoalbuminemia, elevated lactate dehydrogenase, glycated hemoglobin, and C-reactive protein levels are more pronounced in subjects with type 2 diabetes and cancer. Conclusions: The presence of diabetes negatively affects the clinical and biological prognosis of cancer patients.