[The results of the use of a combined probiotic (Lactobacillus rhamnosus GG and Bifidobacterium animalis spp. lactis ВB-12) in children with gastrointestinal and skin manifestations of food allergy].

At present, there are sufficient data on the influence of the gut microbiome on the development of food allergy and its progression. Changes in gut microbiome composition could positive impact on the course of allergic diseases by means of regulating the ratio of pro- and anti-inflammatory cytokines, as well as immunoglobulin E level. The purpose of the research was to study the effectiveness of combined probiotic in treatment of food allergies in children. Material and methods. The prospective randomized controlled study included 92 children aged from 4 to 5 years with symptoms of food allergy, involving the skin and gastrointestinal tract. The main group (n=46) took two chewable tablet Bifiform Kids (Lactobacillus rhamnosus GG >1x109 CFU, Bifidobacterium animalis spp. lactis BB-12 >1x109 CFU, thiamine mononitrate 0.40 mg, pyridoxine hydrochloride 0.50 mg per tablet) 2 times per day during 21 days. The control group (n=46) did not take the complex. The dynamics of the severity of food allergy skin symptoms was assessed using the SCORAD index, of gastrointestinal manifestations - on a point scale after 21 days and after 4 and 6 months (visits 2, 3 and 4). The concentration of immunoglobulin E, interleukins IL-17 and IL-10 was determined by enzyme immunoassay in blood serum at the baseline, as well as after 21 days and after 6 months (visits 1, 2 and 4) after the study initiation. Results. The SCORAD index among children from the main group decreased from 12.4±2.3 до 7.6±1.8 (р=<0.05) while taking a combined probiotic. It was significantly lower (р=<0.05) compared to the control group (SCORAD index changed from 12.1±2.4 to 12.2±1.9). On the 21st day, a statistically significant decrease in level of pro-inflammatory IL-17 (by 27%) and a statistically significant increase in the concentration of anti-inflammatory IL-10 (by 38.9%) were recorded. In children from the main group, the severity of such gastrointestinal symptoms as pain, rumbling in the abdomen, belching with air, bloating, gas discharge, increased stool and its unformularity, decreased compare to the control group of patients (р=<0.05), in which the intensity of complaints related to gastrointestinal manifestations did not change. In the main group of patients, the most clinical efficacy was noted immediately after the end of the probiotic intake. In the following five months, the intensity of symptoms increased in individual subjects from the main group, but in general, the intensity of complaints remained significantly lower than before probiotic intake (р=<0.05). Children from the main group showed a significant decrease in IgE level from 184±121 kU/l by 43.5% at visit 2 and by 38.0% at visit 4 (p=<0.05), while in children from the control group its level didn't change, amounting to 176±141, 165±121 and 178±132 kU/l, respectively. Conclusion. The results of the study show the effectiveness of the use of a combined probiotic (Lactobacillus rhamnosus GG, Bifidobacterium animalis spp. lactis ВB-12) with vitamins B1 and B6 in children with mild forms of gastrointestinal and skin manifestations of food allergy, both in relation to the severity reduction of the clinical symptoms of the disease (skin manifestations, pain, rumbling in the abdomen, belching with air, bloating, gas discharge, increased stool and its unformularity), and in relation to the dynamics of biochemical parameters - a decrease in the level of IgE.

[Effect of 6-month S-methylmethionine intake on the quality of life and dyspepsia symptoms in patients with chronic gastritis].

S-methylmethionine (methylmethionine sulfonium chloride), better known as vitamin U, is a metabolic substrate that affects many metabolic processes in the human organism. Since its discovery, a large number of studies has been produced demonstrating its safety and effectiveness in various diseases, especially in diseases of the gastrointestinal tract. The purpose of the study was to evaluate the effect of methylmethionine sulfonium chloride (vitamin U) intake on the symptoms of dyspepsia and the quality of life of patients with chronic gastritis. Material and methods. The study included 37 patients (21 men and 16 women) aged 35-60 years with chronic gastritis of various etiologies. After inclusion in the study, all patients were prescribed S-methylmethionine at a dose of 300 mg per day. Clinical manifestations of dyspepsia were assessed using the GSRS questionnaire (Gastrointestinal Symptom Rating Scale), quality of life was assessed using the SF 36 questionnaire. The survey was conducted before the start of the therapy, after 3 and 6 months of complex diet therapy. Results. The most pronounced manifestations were dyspeptic (from 3 to 9 points) and diarrheal syndromes (from 2 to 5 points). Other indicators of the GSRS scale did not exceed 4 points. The total score was 15 points. By the 3rd month of therapy, there was a statistically significant decrease in the total score to 9 points (p<0.05). By the 6th month of therapy, the total GSRS score averaged 5.5 points (p<0.05). According to the SF 36 questionnaire, by the end of the 3rd month of therapy, indicators such as PF - physical functioning, BP - Bodily pain and SF - social functioning improved. By the end of the 6th month of therapy, several other indicators also improved (RP - role-physical functioning, GH - general perception of health, VT - viability, RE - Role-Emotional; MH - mental health) (p<0.05). Conclusion. The study showed that the appointment of dietary supplements containing methylmethionine sulfonium chloride at a dose of 300 mg per day helps to reduce the severity of dyspeptic symptoms in patients with chronic gastritis and their quality of life.

[CLINICAL DIAGNOSTIC VALUE OF OXIDATIVE STRESS MARKERS IN PATIENTS WITH CHRONIC HEART FAILURE. OPPORTUNITIES OF THEIR PHARMACOLOGICAL CORRECTION BY ETOXIDOL].

Purpose - to evaluate the effectiveness of a fundamentally new antioxidant drug Amoxidal malate in patients with chronic heart failure (CHF) and its effect on marker of oxidative stress 2,3-diphosphoglycerate -2,3-DPG regulating the dissociation of oxyhemoglobin into hemoglobin and oxygen depending on the partial pressure of oxygen in the lungs and effect on other markers of oxidative stress. Clinical study of etoxazole was conducted in the city hospital N 23. 32 people were examined. At the age of 55 to 76 years (men and women) with coronary heart disease, stable angina, who had a myocardial infarction with a diagnosis of chronic heart failure II-IU FC according to the NYHA classification. Hypertension was diagnosed in 15 patients and type 2 diabetes mellitus in 8 patients. The study included patients with an ejection fraction of less than 40%. Permanent atrial fibrillation was diagnosed in 6 patients. Patients were divided into 2 groups: 1 main group, 22 patients who were added to the standard therapy with intravenous infusions of Ethylmethylhydroxypyridine malate, 2 group - control group, 10 people who received standard pharmacotherapy of CHF. Indicators of oxidative status, especially 2,3-DPH, were evaluated. and also, the voltage of oxygen (pO2), pCO2, pH, concentration of superoxide dismutase (SOD), malondialdehyde (MDA), the concentration of total peroxides in the blood of these patients. Etilmetilgidroksipiridinamaalat restores oxygenation of the blood in patients who are intravenously introduced Amoxidal compared with patients not receiving this treatment with CHF IV FK. Analysis comparative assessment of treatment results shows that the addition of Ethoxide to standard therapy is most beneficial effect on patients> IU F. K. the Inclusion of the new Patriotic antioxidant drug Amoxidal in standard therapy of patients with CHF is pathogenetically justified and promising.

[Novel Possibilities in Pharmacotherapy of Patients With Chronic Heart Failure].

In this article we have described clinical pharmacology and data of clinical studies of an innovational drug valsartan + sacubitril in patients with chronic heart failure (CHF). The use of supramolecular complex valsartan + sacubitril allows to elevate quality of life and improve prognosis of patients with CHF. High efficacy of valsartan+sacubitril relative to impact on composite primary end-point (cardiovascular death + hospitalization due to CHF) was demonstrated in the clinical trial PARADIGM-HF in which it was compared with angiotensin converting enzyme inhibitor enalapril. Advantages of the use of valsartan + sacubitril for the budget were demonstrated in pharmacoeconomic studies. These advantages are maximally realized at long-term administration. Cost-efficacy of the use of valsartan+sacubitril in pharmacotherapy of CHF is comparable with that of statins in the treatment of ischemic heart disease or implantation of a cardioverter-defibrillator in prevention of sudden cardiac death. Thus, introduction of the drug into practice can be expected to reduce budget expenditures.

[PERSONALIZED MEDICINE IN INTERNAL MEDICINE].

Personalized medicine - a new direction in medicine, which is based on the study of various biomarkers and the use of new methods of molecular analysis (primarily evaluating the activity of isoenzymes of cytochrome P450), allowing individualized approach to the selection of both the drugs and the selection of the dosing regimen for the purpose of maximize the effectiveness and safety of pharmacotherapy. This personalized medicine is to change the development and use of preventive and curative interventions. Genetic polymorphism isozymes of cytochrome P450 may determine the individual activity of a particular isozyme, and thus, to predict the clinical effectiveness, and in some cases, the risk of adverse reactions. The article is an example of the use of information on the activity of cytochrome P450 in clinical practice in matters of diagnosis, treatment and prevention of diseases. The scheme of the five best-known activity of isoenzymes of cytochrome P450 is shown.

Mandibular Advancement vs CPAP for Blood Pressure Reduction in Patients With Obstructive Sleep Apnea.

BACKGROUND: Hypertension guidelines recommend diagnosis and treatment of obstructive sleep apnea (OSA) in patients with hypertension. The mandibular advancement device (MAD) is an oral appliance therapy for patients who decline or cannot tolerate continuous positive airway pressure (CPAP). OBJECTIVES: We compared the relative effectiveness of MAD vs CPAP in reducing 24-hour ambulatory blood pressure (BP). METHODS: In an investigator-initiated, randomized, noninferiority trial (prespecified margin 1.5 mm Hg), 321 participants aged ≥40 years with hypertension and increased cardiovascular risk were recruited at 3 public hospitals for polysomnography. Of these, 220 participants with moderate-to-severe OSA (apnea-hypopnea index ≥15 events per hour) were randomized to either MAD or CPAP (1:1). The primary outcome was the difference between the 24-hour mean arterial BP at baseline and 6 months. RESULTS: Compared with baseline, the 24-hour mean arterial BP decreased by 2.5 mm Hg (P = 0.003) at 6 months in the MAD group, whereas no change was observed in the CPAP group (P = 0.374). The between-group difference was -1.6 mm Hg (95% CI: -3.51 to 0.24, noninferiority P < 0.001). The MAD group demonstrated a larger between-group reduction in all secondary ambulatory BP parameters compared with the CPAP group, with the most pronounced effects observed in the asleep BP parameters. Both the MAD and CPAP improved daytime sleepiness, with the between-group difference similar (P = 0.384). There were no between-group differences in cardiovascular biomarkers. CONCLUSIONS: MAD is noninferior to CPAP for reducing 24-hour mean arterial BP in participants with hypertension and increased cardiovascular risk. (Cardiosleep Research Program on Obstructive Sleep Apnea, Blood Pressure Control and Maladaptive Myocardial Remodeling-Non-inferiority Trial [CRESCENT]; NCT04119999).

Non-Tuberculous Mycobacterial Cervicofacial Lymphadenitis in Children-10-Year Experience in a Tertiary Pediatric Center.

BACKGROUND: Lymphadenitis is the most common manifestation of non-tuberculous mycobacteria (NTM) infection in children. We describe the epidemiology and clinical characteristics of NTM lymphadenitis, determine diagnostic yield from tissue sampling, and review management and outcomes. METHODS: This was a 10-year retrospective review of children aged 0-16 years diagnosed with NTM cervicofacial lymphadenitis who were seen in a pediatric infectious disease clinic in a tertiary public hospital. Data relating to patient demographics, clinical features, surgical and antimicrobial treatment, complications, and outcomes were retrieved from patients' electronic medical records and analyzed. RESULTS: There were 48 episodes of NTM cervicofacial lymphadenitis in 45 children (17 males and 28 females). Of these episodes, 43.7% manifested as a unilateral single node, mostly parotid (39.6%) and submandibular (29.2%). All patients underwent diagnostic fine-needle aspiration or surgery. Surgical excision more frequently yielded positive histological findings (P = .016). NTM was identified in 22/48 episodes (45.8%) via culture or molecular sequencing. Mycobacterium abscessus was most commonly found (47.8%). Thirty-eight children (79.2%) received antibiotics. Outcomes in 43 episodes revealed full resolution in 69.8%, while 25.6% had de novo disease and 4.6% experienced recurrence at the same site. Overlying skin changes and multiple or bilateral nodal diseases were significantly associated with de novo disease or recurrence (P = .034 and .084, respectively). Complications occurred in 11/70 (15.7%) procedures. Antibiotic-associated adverse effects occurred in 14/38 (36.8%) episodes. CONCLUSIONS: NTM lymphadenitis remains a challenging condition. More aggressive management with surgical excision and antibiotics is recommended for those with overlying skin changes and extensive nodal disease.

Global Registry of Acute Coronary Events Score Underestimates Post-Acute Coronary Syndrome Mortality among Cancer Patients.

Background Patients with prior cancer are at increased risk of acute coronary syndrome (ACS) with poorer post-ACS outcomes. We aimed to ascertain if the Global Registry of Acute Coronary Events (GRACE) score accurately predicts mortality risk among patients with ACS and prior cancer. Methods We linked nationwide ACS and cancer registries from 2007 to 2018 in Singapore. A total of 24,529 eligible patients had in-hospital and 1-year all-cause mortality risk calculated using the GRACE score (2471 prior cancer; 22,058 no cancer). Results Patients with prior cancer had two-fold higher all-cause mortality compared to patients without cancer (in-hospital: 22.8% versus 10.3%, p < 0.001; 1-year: 49.0% vs. 18.7%, p < 0.001). Cardiovascular mortality did not differ between groups (in-hospital: 5.2% vs. 4.8%, p = 0.346; 1-year: 6.9% vs. 6.1%, p = 0.12). The area under the receiver operating characteristic curve of the GRACE score for prediction of all-cause mortality was less for prior cancer (in-hospital: 0.64 vs. 0.80, p < 0.001; 1-year: 0.66 vs. 0.83, p < 0.001). Among patients with prior cancer and a high-risk GRACE score > 140, in-hospital revascularization was not associated with lower cardiovascular mortality than without in-hospital revascularization (6.7% vs. 7.6%, p = 0.50). Conclusions The GRACE score performs poorly in risk stratification of patients with prior cancer and ACS.

A quantum ruler for orbital magnetism in moiré quantum matter.

For almost a century, magnetic oscillations have been a powerful "quantum ruler" for measuring Fermi surface topology. In this study, we used Landau-level spectroscopy to unravel the energy-resolved valley-contrasting orbital magnetism and large orbital magnetic susceptibility that contribute to the energies of Landau levels of twisted double-bilayer graphene. These orbital magnetism effects led to substantial deviations from the standard Onsager relation, which manifested as a breakdown in scaling of Landau-level orbits. These substantial magnetic responses emerged from the nontrivial quantum geometry of the electronic structure and the large length scale of the moiré lattice potential. Going beyond traditional measurements, Landau-level spectroscopy performed with a scanning tunneling microscope offers a complete quantum ruler that resolves the full energy dependence of orbital magnetic properties in moiré quantum matter.

Trk C signaling is required for retinal progenitor cell proliferation.

Although neurotrophin actions in the survival of specific retinal cell types have been identified, the biological functions for neurotrophin-3 (NT-3) in early retinal development remain unclear. Having localized NT-3 and trk C expression at early developmental stages when retinal neuroepithelial progenitor cells predominate, we sought to modulate NT-3 signaling in these cells by overexpressing a truncated isoform of the NT-3 receptor, trk C. We have demonstrated that this non-catalytic receptor can inhibit NT-3 signaling when coexpressed with the full-length kinase-active trk C receptor. Using a replication-deficient retrovirus to ectopically express the truncated trk C receptor to limited numbers of progenitor cells in ovo, we examined the effects of disrupted trk C signaling on the proliferation or differentiation of retinal cells. Clones expressing truncated trk C exhibited a 70% reduction in clone size, compared with clones infected with a control virus, indicating that inhibition of trk C signaling decreased the clonal expansion of cells derived from a single retinal progenitor cell. Additionally, impaired NT-3 signaling resulted in a reduction of all retinal cell types, suggesting that NT-3 targets retinal precursor cells rather than differentiated cell types. BrdU labeling studies performed at E6 indicate that this reduction in cell number occurs through a decrease in cell proliferation. These studies suggest that NT-3 is an important mitogen early in retinal development and serves to establish the size of the progenitor pool from which all future differentiated cells arise.

Paediatric anaphylaxis in a Singaporean children cohort: changing food allergy triggers over time.

BACKGROUND: We have noticed changes in paediatric anaphylaxis triggers locally in Singapore. OBJECTIVE: We aimed to describe the demographic characteristics, clinical features, causative agents and management of children presenting with anaphylaxis. METHODS: This is a retrospective study of Singaporean children presenting with anaphylaxis between January 2005 and December 2009 to a tertiary paediatric hospital. RESULTS: One hundred and eight cases of anaphylaxis in 98 children were included. Food was the commonest trigger (63%), followed by drugs (30%), whilst 7% were idiopathic. Peanut was the top food trigger (19%), followed by egg (12%), shellfish (10%) and bird's nest (10%). Ibuprofen was the commonest cause of drug induced anaphylaxis (50%), followed by paracetamol (15%) and other nonsteroidal anti-inflammatory drugs (NSAIDs, 12%). The median age of presentation for all anaphylaxis cases was 7.9 years old (interquartile range 3.6 to 10.8 years), but food triggers occurred significantly earlier compared to drugs (median 4.9 years vs. 10.5 years, p < 0.05). Mucocutaneous (91%) and respiratory features (88%) were the principal presenting symptoms. Drug anaphylaxis was more likely to result in hypotension compared to food anaphylaxis (21.9% vs. 2.7%, Fisher's exact probability < 0.01). There were 4 reported cases (3.6%) of biphasic reaction occurring within 24 h of anaphylaxis. CONCLUSION: Food anaphylaxis patterns have changed over time in our study cohort of Singaporean children. Peanuts allergy, almost absent a decade ago, is currently the top food trigger, whilst seafood and bird's nest continue to be an important cause of food anaphylaxis locally. NSAIDs and paracetamol hypersensitivity are unique causes of drug induced anaphylaxis locally.