Peculiarities of response to basic anti-inflammatory therapy of schoolchildren with alternative inflammatory phenotypes of bronchial asthma

Purpose — to evaluate the effectiveness of long-term anti-inflammatory therapy with inhaled glucocorticosteroids in children with alternative inflammatory phenotypes of bronchial asthma (BA) for the development of individualized control treatment. Materials and methods. A comprehensive survey of 94 school-age children with BA was conducted. According to the results of cytological examination of sputum, 2 clinical observation groups were formed. The first group of patients was formed by 38 patients with non3eosinophilic (neutrophilic) nature of the inflammatory process of the bronchi (mean age — 11.1±2.9 years, the proportion of boys — 52.6±8.1%), and the second group — 56 children with eosinophilic type of airway inflammation (3% or more of eosinophilic granulocytes in sputum), ie eosinophilic asthma phenotype (mean age — 12.2±3.2 (P>0.05) years, the proportion of boys — 67.9±6.2%, P>0.05). According to the main characteristics of the observation group could be compared. All patients underwent a comprehensive clinical and paraclinical (spirographic) examination. Scoring control of BA symptoms was performed using a questionnaire at the beginning and at the end of the course of anti-inflammatory basic therapy. The questionnaire included the clinical signs of BA reflected in the scores, which were evaluated by patients and their parents, as well as the scale of instrumental studies according to the spirographic examination of patients. Results. The paper shows that the best effect of long-term courses of basic therapy with inhaled glucocorticosteroids (ICS) was observed in patients with eosinophilic airway inflammation. Thus, the share of patients with a relatively satisfactory level of clinical control of the disease and with close to normal spirographic indicators was in group II: before the course of treatment with inhaled corticosteroids 25.0% and 31.9%, and after treatment — 81.3% (P<0,01) and 69.0% (P<0.01), respectively. Thus, an increase of 69.3% in relative risk (IRR) and 56.3% in absolute risk (IAR) of BA control reflected a pronounced control effect of inhaled corticosteroids in the eosinophilic nature of airway inflammation. The minimum number of patients needed to treat (NNT) in order to obtain at least one positive result was 2. At the same time, in patients with neutrophilic inflammatory process, the proportion of patients with a relatively satisfactory level of clinical and paraclinical (according to spirography) disease control was: before the appointment of ICS — 30.8% and 30.8%, and after treatment — 50% (PFisher's exact test>0.05) and 76.9% (PFisher's exact test<0.01), respectively. This persistence of clinical manifestations of the disease indicated an insufficient level of control of non3eosinophilic BA in the treatment of inhaled corticosteroids and questioned the feasibility of monotherapy with this group of neutrophilic bronchitis. The insufficient effect of anti3inflammatory therapy with inhaled corticosteroids was evidenced by the fact that IRR of satisfactory level of clinical control was 38.4%, IAR — 19.2%, and NNT — 6 patients. Conclusions. In patients with the eosinophilic phenotype of BA, the use of long courses of inhaled glucocorticosteroids led to an increased chance of achieving disease control, while the chances of improving of the pulmonary function tests were also observed in the neutrophilic phenotype of the disease. The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local ethics committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: bronchial asthma, children, basic anti-inflammatory therapy.

A Randomised Clinical Control Study to Evaluate the Efficacy of Shodhita Kuchla Powder (Purified Strychnos Nux-Vomica L.) and Brahmi Extract (Bacopa Monnieri L. Pennell) on Klaibya (Dhwajbhang) w.s.r. to Erectile Dysfunction

Klaibya is defined in Ayurveda as the inability to achieve and maintain sufficient rigidity in the penis, which is essential for his sexual urges or the needs of his female partner during sexual activity. Chakrapani limits the concept of Klaibya to merely erectile dysfunction. Dhwajbhang, according to Acharya Sushruta, is a form of Klaibya caused by excessive coitus. The standard initial evaluation of a man experiencing ED is conducted in person and involves sexual, medical, and psychosocial histories, as well as laboratory tests comprehensive enough to identify comorbid diseases that may predispose the patient to ED and may contraindicate particular treatments. Properties of Ayurvedic drug; Kuchla (Strychnos nux-vomica) in classical text Rasatarangani as therapeutic of Klaibya (ED) and Brahmi (Bacopa monnieri) is well known Medhya drug that works on neuro- psychological disorders. The current study evaluated the effects of Kuchla and Brahmi on 36 erectile dysfunction patients, having 30 of them completing the trial. The patients were categorized into two parts: Group A administered an ED 250 capsule (Hypothetical) once a day (250mg) with milk, and Group B received a placebo once a day with milk HS for 30 days, followed by another 30 days.

The KOALA-study: study protocol for a comprehensive study of cognitive biases in adolescent anorexia nervosa patients compared to healthy and clinical controls

Background Anorexia nervosa (AN) is characterized by dysfunctional cognitions including cognitive biases at various levels of information processing. However, less is known about the specificity of these biases, i.e., if they occur for eating-disorder-related information alone or also for non-eating-disorder-related emotional information in AN patients (content-specificity) and if they are unique to individuals with AN or are also shown by individuals with other mental disorders (disorder-specificity). Methods The present study systematically assesses cognitive biases in 12–18-year-old female adolescents with AN on three levels of information processing (attention, interpretation, and memory) and with regard to two types of information content (eating-disorder-related, i.e., stimuli related to body weight and shape, and non-eating-disorder-related). To address not only content- but also disorder-specificity, adolescents with AN will be compared not only to a healthy control group but also to a clinical control group (adolescents with major depression or particular anxiety disorders). Cognitive biases are assessed within a single experimental paradigm based on the Scrambled Sentences Task. During the task eye movements are recorded in order to assess attention biases while interpretation biases are derived from the behavioural outcome. An incidental free recall test afterwards assesses memory biases. We expect adolescents with AN to show more pronounced negative cognitive biases on all three levels of information processing and for both types of content compared to healthy adolescents. In addition, we expect the specificity of biases to translate into differential results for the two types of content: AN patients are expected to show stronger biases for disorder-related stimuli but similar or less pronounced biases for non-disorder-related stimuli compared to the clinical control group. Discussion This is the first study to comprehensively assess cognitive biases in adolescents with AN. It will have essential implications not only for cognitive-behavioural models of AN but also for subsequent studies aiming to modify cognitive biases in this population, thereby addressing important maintaining factors already at an early stage of the disorder.

Anti-infective Agents

Certain bacterial, protozoal, and viral infections remain the most frequent infectious diseases causing morbidity and death globally. However, the development of new drugs for the treatment of such infectious diseases has been slow, although some promising drugs have been developed and used for clinical control of such intractable infections. For example, antiviral drugs, including remdesivir and favipiravir, are currently used for the clinical treatment of coronavirus disease 2019 (COVID-19) patients. Notably, these drugs have been developed based on the drug repositioning technique. In addition, some immune-regulatory drugs, including corticosteroids, baricitinib and tocilizumab, help reduce inflammation in the body since inflammation can lead to some of the more severe symptoms of COVID-19 patients. However, at present, we have substantially no new drugs, which act on metabolic reactions by specifically inhibiting viral proteins of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in host cells. Only recombinant antibodies specific to spike proteins of the coronavirus, such as bamlanivimab, etesevimab, casirivimab, and imdevimab, have been approved or are in the development for clinical use as immune-adjunctive treatment of COVID-19 patients with mild symptoms. In this context, the drug design based on quantitative structureactivity relationship (QSAR) analysis, especially three-dimensional-QSAR, may be very beneficial for the development of SARS-CoV-2- specific chemotherapeutic anti-infective agents [1]. ...

Polymorphic variants of proteasomal genes PSMA3 and PSMA6 in children with articular syndrome and juvenile idiopathic arthritis

A comparative analysis of three single nucleotide variations of the proteasomal genes PSMA3 (rs2348071) and PSMA6 (rs2277460 and rs1048990) was carried out in the groups of children from 1 to 16 years old with the autoimmune rheumatic disease - juvenile idiopathic arthritis (JIA; n = 199), with articular syndrome of non-autoimmune etiology (n = 229) and in the clinical control group with neither autoimmune nor chronic inflammatory diseases (n = 379). PCR, PCR–RFLP and real-time PCR were used for genotyping. It was found that the CG genotype and G allele of rs10489990 polymorphism (OR = = 1.93; 95 % CI 1.29-2.90; p = 0.002 and OR = 1.51; 95 % CI 1.11-2.04; p = 0.008 respectively), as well as the AA genotype of rs2348071 polymorphism (OR = 1.89; 95 % CI 1.02–3.49; p = 0.044) are associated with the JIA susceptibility, but not with articular syndrome. The established JIA risk genotypes may indicate the involvement of PSMA3 and PSMA6 genes in the development of an autoimmune reaction. In combination with other risk DNA markers, they can be proposed to assess a genetic predisposition to JIA. It was also revealed that the frequencies of risk genotypes and alleles for JIA in the group of patients with articular syndrome as a whole occupy an intermediate position between JIA and control group frequencies. This may indicate an increased JIA risk in some patients with articular syndrome.

Manual Segmentation of 12 Layers of the Retina and Choroid through SD-OCT in Intermediate AMD: Repeatability and Reproducibility

Purpose: To evaluate the repeatability and reproducibility of the segmentation of 12 layers of the retina and the choroid, performed manually by SD-OCT, along the horizontal meridian at three different temporal moments, and to evaluate its concordance with the same measurements performed by two other operators in intermediate AMD. Methods: A cross-sectional study of 40 eyes from 40 subjects with intermediate AMD was conducted. The segmentation was performed manually, using SD-OCT. The 169 measurements per eye were repeated at three time points to study the intra-operator variability. The same process was repeated a single time by two different trained operators for the inter-operator variability. Results: Forty participants (28 women and 12 men) were enrolled in this study, with an average age of 76.4 ± 8.2 (range, 55–92 years). Overall, the maximum values of the various structures were found in the 3 mm of the macula. Intra-operator variability: the highest ICC values turned out to be discovered in thicker locations. Inter-operator variability: except correlation values of 0.826 (0.727; 0.898) obtained in the OPL (T2.5) and 0.634 (0.469; 0.771) obtained in the IPL (N2), all other correlation values were >0.92, in most cases approaching higher values like 0.98. Conclusion: The measurements of several layers of the retina and the choroid achieved at 13 locations presented a good repeatability and reproducibility. Manual quantification is still an alternative for the weaknesses of automatic segmentation. Locations of greatest concordance should be those used for the clinical control and monitoring.

Small airway dysfunction and poor asthma control: a dangerous liaison

Asthma is a common chronic condition, affecting approximately 339 million people worldwide. The main goal of the current asthma treatment guidelines is to achieve clinical control, encompassing both the patient symptoms and limitations and the future risk of adverse asthma outcomes. Despite randomized controlled trials showing that asthma control is an achievable target, a substantial proportion of asthmatics remain poorly controlled in real life. The involvement of peripheral small airways has recently gained greater recognition in asthma, and many studies suggest that the persistent inflammation at these sites leads to small airway dysfunction (SAD), strongly contributing to a worse asthma control. Overall, the impulse oscillometry (IOS), introduced in the recent years, seems to be able to sensitively assess small airways, while conventional spirometry does not. Therefore, IOS may be of great help in characterizing SAD and guiding therapy choice. The aim of this article is to review the literature on SAD and its influence on asthma control, emphasizing the most recent evidence.

SURGICAL TREATMENT IN RAYNAUD'S DISEASE

INTRODUCTION In primary or refractory cases of Raynaud's Disease (RD), with severe symptoms (pain, ulcers, and disability), minimally invasive surgical treatments such as thoracoscopic sympathectomy have recently been proposed. The objective of this study will be to evaluate the viability, feasibility and results of this therapeutic option in this type of patient. MATERIAL AND METHODS Descriptive prospective study from January 2017 to January 2019 where all patients with a diagnosis of RD, with poor clinical control and disability, and refractory to medical treatment are collected. RESULTS Seven girls (9-15 years old) were collected. All underwent bilateral thoracoscopic sympathectomy, T2-T4, with a mean surgical time of 55 min. No need for pleural drainage. All of them were discharged before 36 hours after surgery (12-36 hours) without any immediate intra or postoperative complications. All reported an immediate postoperative period without incident, without new episodes of pain or intense vasoconstriction. However, 6 months after surgery, 3 of the 7 (42.85%) presented partial reappearance of the symptoms. However, the 7 presented 100% satisfaction with the surgical results. CONCLUSIONS There are currently very few published studies regarding this surgical option. We believe that our series is the first pediatric series to be collected, although it is very limited. However, the results obtained to date, in global terms, are encouraging. We consider that thoracoscopic sympathectomy is a feasible and safe surgical technique to consider in patients with RD refractory to conservative treatment.