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Exosome in cardiovascular diseases: a complex world full of hope
Exosomes are a subgroup of extracellular vesicles containing a huge number of bioactive
molecules. They represent an important means of cell communication, mostly between different
cell populations, with the purpose of maintaining tissue homeostasis and coordinating the adaptive
response to stress. This type of intercellular communication is important in the cardiovascular field,
mainly due to the fact that the heart is a complex multicellular system. Given the growing interest
in the role of exosomes in cardiovascular diseases and the numerous studies published in the last
few decades, we focused on the most relevant results about exosomes in the cardiovascular filed
starting from their characterization, passing through the study of their function, and ending with
perspectives for their use in cardiovascular therapies
Povezanost izraženosti rezistina s histološkom slikom aterosklerotskoga plaka [Expression of resistin in atherosclerotic plaque]
The principal aim of this study was to investigate the correlation between serum and atherosclerotic plaque expression of resistin and clinical symptomatology as well as histological features of atherosclerotic plaque. The study included 78 patients with significant (>60 %) unilateral stenosis of carotid artery hospitalized due to carotid endarterectomy. Patients were divided into two groups based on clinical symptoms. Based on the histological features, the plaques were divided into groups I-VIII according AHA classification and into groups with unstable and stable plaque phenotype.
Immunohistochemistry was performed with the primary antibody for human resistin (Resistin/RETN antibody, eBioscience), and the resistin expression was determined semi-quantitatively. The serum concentration of resistin was determined by the ELISA method.
A confirmed hypothesis that expression of resistin is higher in unstable plaques indicates its association with the plaque destabilization process and suggests that resistin could potentially be used as one of the histological markers of plaque instability. Significant correlation of resistin with the symptoms of the patient also indicates potential utilization of resistin to stratify high-risk patients. Further research will be required to detect potential drugs whose purpose would be to reduce serum resistin values and consequently reduce cardiovascular risk
Cystic fibrosis presentation in del. F508 and p. Tyr109Glyfs compound heterozygote CFTR state: a case report
The diagnosis of cystic fibrosis (CF) is commonly confirmed by molecular genetics with the presence of specific mutations of cystic fibrosis transmembrane conductance regulator (CFTR) gene. We report a case of cystic fibrosis (CF) in a 15-year-old female patient who is a compound heterozygote for CFTR gene, with delta F508 and Tyr109Glyfs mutations detected. This is the first detailed description of such a case in the medical literature. The primary CF presentation occurred at the age of 9 in the form of gastrointestinal symptoms including greasy, bulky, and foul-smelling stool. The patient exhibited delayed growth, with her height and weight being below the 5th centile for age according to the World Health Organization growth curves. Pancreatic enzyme supplement treatment was started immediately, alongside high-fat and high-calorie diet, resulting in patient's recovery and development. DNA analysis of CFTR gene demonstrated the presence of del. F508 mutation and a rare combining deletion and insertion mutation p. Tyr109Glyfs. The combination of the two mutations is very rare in CF patients and is therefore valuable to document this case in order to provide information on disease progression, therapy options, and outcomes. With standard treatment and early diagnosis, the patient is currently doing well and is not restricted by the disease in her daily and sports activities
Position statement for the diagnosis and management of anogenital warts
Background: Anogenital warts (AGW) can cause economic burden on healthcare systems and are associated with emotional, psychological and physical issues.
----- Objective: To provide guidance to physicians on the diagnosis and management of AGW.
----- Methods: Fourteen global experts on AGW developed guidance on the diagnosis and management of AGW in an effort to unify international recommendations. Guidance was developed based on published international and national AGW guidelines and an evaluation of relevant literature published up to August 2016. Authors provided expert opinion based on their clinical experiences.
----- Results: A checklist for a patient's initial consultation is provided to help physicians when diagnosing AGW to get the relevant information from the patient in order to manage and treat the AGW effectively. A number of frequently asked questions are also provided to aid physicians when communicating with patients about AGW. Treatment of AGW should be individualized and selected based on the number, size, morphology, location, and keratinization of warts, and whether they are new or recurrent. Different techniques can be used to treat AGW including ablation, immunotherapy and other topical therapies. Combinations of these techniques are thought to be more effective at reducing AGW recurrence than monotherapy. A simplified algorithm was created suggesting patients with 1-5 warts should be treated with ablation followed by immunotherapy. Patients with >5 warts should use immunotherapy for 2 months followed by ablation and a second 2-month course of immunotherapy. Guidance for daily practice situations and the subsequent action that can be taken, as well as an algorithm for treatment of large warts, were also created.
----- Conclusion: The guidance provided will help physicians with the diagnosis and management of AGW in order to improve the health and quality of life of patients with AGW
Antimikrobni peptidi u bronhoalveolnom ispirku djece s infekcijom donjih dišnih putova uzrokovanom respiratornim sincicijskim virusom [Antimicrobial peptides in bronchoalveolar lavage fluid in children with respiratory syncytial virus lower respiratory tract infection]
Objective: To investigate the role of antimicrobial peptides HNP1-3, HBD1, HBD2, HBD4 and LL-37 in children with respiratory syncytial virus lower respiratory tract infection. -----
Patients and methods: Antimicrobial peptides levels were measured by immunosorbent assay in bronchoalveolar lavage fluid in 21 children with respiratory syncytial virus infection (of whom nine had bacterial superinfection) and nine healthy children. -----
Results: Unadjusted comparisons indicated significantly higher HBD1, HBD2, HNP1-3 and LL-37 concentrations in bronchoalveolar lavage fluid in children with RSV infection vs. controls. Univariate association between BAL concentration of HBD2 and disease severity indicator was found – higher concentrations were associated with higher PaO2/fiO2 min. The association remained significant after adjustment. -----
Conclusion: Antimicrobial peptides HNP1-3, HBD1, HBD2 and LL-37 play an important role in respiratory syncytial virus lower respiratory tract infection in children. HBD2 stands out among them with a definite protective role
Učinak terapijskih vježbi propriocepcije na bol i funkcionalnu sposobnost u usporedbi sa standardnim vježbama u bolesnika s osteoartritisom koljena
The aim of this study was to evaluate the effects of a combined standard exercise program in addition of proprioceptive exercise on pain and functional abilities in people with knee osteoarthritis (OA) compared to the standard exercise program alone. The prevalence of knee and hip OA has the largest growth in the world among musculoskeletal diseases. One of the frequent symptoms and signs of knee OA is disrupted proprioception. Knee proprioception is derived from the integration of afferent signals from the proprioceptivereceptors of different knee structures (muscles, capsule, tendons,ligaments, skin), and is also influenced by the signal outside the knee (eg. vestibular organ, visual system, skin and proprioceptive receptors from other parts of the body). It serves to protect against harmful injuries and is important for maintaining common stability and for normal joint coordination during movement. Defective proprioceptive sensation can result in distorted balance affecting functionality and is the main cause of loss of autonomy. According to the recommendations of the European Ligue Against Rheumatism - EULAR, physical therapy is included in the non-surgical and nonpharmacological therapy of patients with OA knee, and is part of all guidelines for its treatment. According to MOVE consensus exercises for hip and knee OA shoud be individually tailored and it is recommended to conduct targeted exercises for specific and potentially reversible lesions that are, for example, common to knee OA and are known to be related to pain and disability. In order to prevent future falls, receptors receiving sensory information from the vestibular, visual and somatosensory apparatus should be improved to activate antigravitational muscles and stimulate balance. Balance and proprioceptive exercises should be equally performed on dry and in water. The effect of both programs that were part of this study was significant in reducing pain intensity over the past 7 days, reducing the impact of pain in daily activities as well as in reducing the global assessment of patient disease activity (GOABB), but the group who additionally conducted proprioceptive exercise showed a tendency for better results as well as continuity of further fall in pain intensity over the past 7 days, and GOABB. More detailed comparison between persons aged 66 to 80 the effect of a program with proprioceptive exercises on the intensity of pain, the impact of pain on ASŽ and GOABB was increased significantly. The effect of both programs was equally significant in reducing the global assessment of doctors' disease activities. By the additional examination of the subjective assessment of pain and functionality, and of the quality of life, both groups achieved improvement, but there were no significant difference between them, with the exception of the tendency for better results of the group with proprioceptive exercises. This group also showed a significant improvement in their own perception of confidence in
activities of daily living after 3 months as well as tendency for better results across all measurements. Both groups have equally improved muscle strength and movement. Clinical balance tests can help to estimate the risk of falling, and / or determine the need for balance rehabilitation as well as the main cause of the balance disorder. Functional balance tests did not show any significant differences between the groups, but both groups had a significant improvement after completing the exercise program, with the tendency of better results in age group of 66 to 80 years. There was no statistically significant difference in the dynamic balance (STAR test), and both groups showed statistically significant improvement in all directions, especially in the posterior direction as well as in the adjacent directions (posteromedial and posterolateral). The proprioceptive test showed a tendency for better results in the group that conducted additional proprioceptive exercises, although both groups had statistically significant improvements in all measurements. The addition of proprioceptive exercise to the standard exercise program can improve the daily locomotion of people with knee OA as well as the standard exercise program with significantly better effect for people aged 66 to 80, so such exercises should be an integral part of the rehabilitation protocol for people with knee OA that age group
Učestalost patološkoga odgovora na ortostatsku provokaciju u bolesnika oboljelih od klinički izoliranoga sindroma [Prevalence of pathological response to orthostatic provocation in patients with clinically isolated syndrome]
Introduction: Autonomic dysfunction is common in people with multiple sclerosis. The aim of this study was to estimate the frequency of pathological response to PP-HUT in people with CIS as well as the correlation of pathological response with localization of demyelinating lesions at MRI, EDSS level, catecholamine values and HRV analysis. -----
Subjects and Methods: Patients older than 18 years of age with CIS diagnosis were included in the study. PP-HUT was performed, blood was taken for catecholamine determination and HRV analyzed using Kubios HRV Standard 3.0.0. Following HRV parameters were analyzed: LF, HF, HF, LF / HF and SDNN. The study also included a group of healthy subjects who had undergone HUT testing without painful stimulation and were included in HRV analysis.
Results: Response to PP-HUT was pathological in 47% of subject. No correlation was found between the incidence of pathological response and localization of demyelinating lesions on the MRI and the degree of disability. There was no difference in HRV between patients with CIS and healthy subjects. Patients with demyelinating brain stem lesions had significantly more frequent sympathetic impairments as expressed by LFtilt. Patients with demyelinating lesions in the brainstem had greater neurological disability as expressed by EDSS compared to patients without lesions in the brainstem. -----
Conclusion: Autonomic nervous system dysfunction is frequent in people with CIS with dominant damage of the sympathetic part
Religiosity and severity of symptoms in Croatian patients with major depressive disorder or schizophrenia
We examined and compared the relationship between religiosity and symptom severity in patients with major depressive disorder (MDD) rated by the Hamilton Depression Rating Scale) and schizophrenia (rated by the Positive and Negative Syndrome Scale). The Duke University Religion Index, the Santa Clara Strength of Religious Faith (SCSORF) questionnaire, and the Brief Religious Coping scale scores were similar between patients with MDD (n = 50) and patients with schizophrenia (n = 50). In patients with MDD, higher organizational religious activity (ORA) (estimate = 2.28, 95% confidence interval [CI] = 0.37-4.19; p = 0.020) and higher negative religious coping (estimate = 0.43, 95% CI = 0.03-0.84; p = 0.037) were independently associated with more severe symptoms. In patients with schizophrenia, higher ORA was associated with lower negative symptoms (estimate = -1.99, 95% CI = -3.94 to -0.03; p = 0.046). Higher SCSORF was associated with lower ORA in both patient subsets, and thus indirectly with milder symptoms in patients with MDD and with more severe negative symptoms in patients with schizophrenia. The relationship between religiosity and symptom severity apparently differs in patients with MDD and those with schizophrenia
Effect of food intake on hemodynamic parameters during the tilt-table test in patients with postural orthostatic tachycardia syndrome
BACKGROUND AND PURPOSE:
The aim of this study was to determine the effect of food intake on the heart rate (HR) in postural orthostatic tachycardia syndrome (POTS). ----- METHODS:
The following five-phase protocol was applied to 41 subjects who had a sustained HR increment of ≥30 beats/min within 10 min of standing in an initial tilt-table test: 1) 10-min supine phase, 2) 10-min 70°-tilted phase, 3) ingestion of 400 mL of Nutridrink Multi Fibre®, 4) 45-min supine phase, and 5) 10-min 70°-tilted phase. Subjects were divided into four groups: A) difference in HR for standing vs. supine (ΔHR) before the meal of ≥30 beats/min (n=13), B) ΔHR <30 beats/min before the meal but ≥30 beats/min after the meal (n=12), and C) ΔHR <30 beats/min both before and after the meal (n=16). Group D consisted of 10 healthy subjects. ----- RESULTS:
Before the meal, ΔHR was significantly higher in group A than in all of the other groups, and in group B than in group D (p<0.001). After the meal, ΔHR was significantly higher in groups A and B (p<0.001 and p<0.0001, respectively). When we pooled patients (according to their symptoms) from group A and B into a POTS group and from group C and D into a non-POTS group, an increase in HR of 25 beats/min before the meal had a sensitivity of 92.0% and a specificity of 80.8%. After the meal, an increase in HR of 30 beats/min had a sensitivity of 96.0% and a specificity of 96.2%. ----- CONCLUSIONS:
Food intake can significantly alter the results of the tilt-table test and so should be taken into account when diagnosing POTS
The protracted maturation of associative layer IIIC pyramidal neurons in the human prefrontal cortex during childhood: a major role in cognitive development and selective alteration in autism
The human specific cognitive shift starts around the age of 2 years with the onset of self-awareness, and continues with extraordinary increase in cognitive capacities during early childhood. Diffuse changes in functional connectivity in children aged 2-6 years indicate an increase in the capacity of cortical network. Interestingly, structural network complexity does not increase during this time and, thus, it is likely to be induced by selective maturation of a specific neuronal subclass. Here, we provide an overview of a subclass of cortico-cortical neurons, the associative layer IIIC pyramids of the human prefrontal cortex. Their local axonal collaterals are in control of the prefrontal cortico-cortical output, while their long projections modulate inter-areal processing. In this way, layer IIIC pyramids are the major integrative element of cortical processing, and changes in their connectivity patterns will affect global cortical functioning. Layer IIIC neurons have a unique pattern of dendritic maturation. In contrast to other classes of principal neurons, they undergo an additional phase of extensive dendritic growth during early childhood, and show characteristic molecular changes. Taken together, circuits associated with layer IIIC neurons have the most protracted period of developmental plasticity. This unique feature is advanced but also provides a window of opportunity for pathological events to disrupt normal formation of cognitive circuits involving layer IIIC neurons. In this manuscript, we discuss how disrupted dendritic and axonal maturation of layer IIIC neurons may lead into global cortical disconnectivity, affecting development of complex communication and social abilities. We also propose a model that developmentally dictated incorporation of layer IIIC neurons into maturing cortico-cortical circuits between 2 to 6 years will reveal a previous (perinatal) lesion affecting other classes of principal neurons. This "disclosure" of pre-existing functionally silent lesions of other neuronal classes induced by development of layer IIIC associative neurons, or their direct alteration, could be found in different forms of autism spectrum disorders. Understanding the gene-environment interaction in shaping cognitive microcircuitries may be fundamental for developing rehabilitation and prevention strategies in autism spectrum and other cognitive disorders