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BackgroundMontelukast has shown potential as a candidate treatment for dengue. This study aimed to evaluate the efficacy and safety of montelukast in preventing dengue with warning signs.MethodsThis multicenter, randomized, double-blind, placebo-controlled trial enrolled adult participants with NS1 antigenemia in Thailand. The participants were randomly assigned to receive either oral montelukast (10 mg) or a placebo for 10 days or until all symptoms resolved.ResultsBetween January 2021 and June 2023, 358 participants were enrolled and randomly assigned (1:1) to receive either montelukast or placebo. The incidence rate of warning signs in the montelukast group and the placebo group were 9.5% and 7.8% per day, respectively. There was no difference between the two groups (HR 1.36; 95%CI 0.94-1.96, P = 0.105). No statistically significant differences were observed in the incidence rate of severe dengue, hemoconcentration, thrombocytopenia, admission, or recovery from dengue. Neither dengue shock, nor mortality occurred. The montelukast group exhibited a decreased incidence rate of transaminase elevations (0.7% vs 1.4% per day, HR: 0.48, 95%CI 0.25-0.90, P = 0.023).ConclusionOral montelukast does not reduce the incidence of warning signs among patients with dengue. Nevertheless, the observed decrease in transaminase elevations warrants further investigation to evaluate the potential effect of montelukast.Clinical trials registrationClinicaltrials.gov, NCT04673422, registered on 9 December 2020.

Background: The benefits of contact tracing in health care workers (HCWs) and patients in hospital have rarely been evaluated. This study aimed to assess the yield of contact tracing in order to evaluate the usefulness of resource utilization. Methods: Data were collected from 1 April 2021 to 31 March 2022 at teaching hospital in Thailand. The team was notified if any HCW or patient admitted outside COVID-19 designated areas were tested positive. Those with high-risk exposure identified by the team needed to leave from work for 14 days and 2 PCR tests as early as possible and day 14 after the exposure. Result: A total of 4,292 HCWs and 422 patients were exposed to 575 COVID-19 cases and were identified as high-risk contacts, leading to 50,312 days of quarantine and 9,333 PCR tests. The secondary attack rate was 3.42%, which was more common in patients than in HCWs (OR = 1.82, 95%CI = 1.17–2.85, p = 0.0082). Close contact with patients had more secondary attack rates than with HCWs (OR = 1.51, 95%CI:1.01–2.25, p = 0.045). Among those who had close contact with patients, patients but not HCWs had increased risk of infection (OR = 2.86; 95%CI:1.24–6.62; p = 0.0138, OR = 1.06; 95%CI:0.63–1.77; p = 0.834, respectively). The positivity rate of high-risk close contact HCWs was 2.28 per 1,000 person-days after contact, as compared to the positivity rate of low-risk close contact with symptoms at 0.35 per 1,000 person-days during the same period. Conclusions: Hospital-based contact tracing could identify more infected HCWs than symptomatic testing alone. Identifying more infected HCWs could potentially prevent infection in both HCWs and patients.

Abstract Objective Staphylococcus aureus nasal carriage screening among hemodialysis patients is not standard practice in Thailand, because of data lacking regarding prevalence and correlation with subsequent infection. We aimed to investigate the prevalence of S. aureus nasal carriage and its association with bloodstream infection among hemodialysis patients. In this prospective multicenter cohort study, participants were screened for S. aureus nasal carriage over 2 consecutive weeks. Incidence of S. aureus bloodstream infection over the next 12 months was observed. Results The prevalence of S. aureus nasal carriage was 11.67%. Incidence of S. aureus bacteremia among participants with and without S. aureus nasal carriage were 7.1% and 3.8%, respectively. The odds ratio for nasal carriage and subsequent bacteremia was 1.96 (95% CI 0.04–21.79; p = 0.553). Survival analysis showed that time to bacteremia among participants in the two groups did not significantly differ (p = 0.531). Prevalence of S. aureus nasal carriage among hemodialysis patients in Thailand was low. Patients presenting with S. aureus nasal carriage did not have increased risk of S. aureus bacteremia after 12-month follow-up. Nasal S. aureus screening and decolonization should not be encouraged in this setting.

Extensively drug-resistant A. baumannii (XDRAB) pneumonia has a high mortality rate in hospitalized patients. One of the recommended treatments is colistin combined with sulbactam; however, the optimal dosage of sulbactam is unclear. In an open-label, superiority, randomized controlled trial, patients diagnosed with XDRAB pneumonia were randomly assigned (1:1) to receive colistin in combination with sulbactam at either 9 g/day or 12 g/day. The primary outcome was the 28-day mortality rate in the intention-to-treat population. A total of 88 patients received colistin in combination with sulbactam at a dosage of either 12 g/day (n = 45) or 9 g/day (n = 43). Trends toward a lower mortality rate were observed in the 12 g/day group at 7 days (11.1% vs. 23.3%), 14 days (33.3% vs. 41.9%), and 28 days (46.7% vs. 58.1%). The microbiological cure rate at day 7 was significantly higher in the 12 g/day group (90.5% vs. 58.1%; p = 0.02). Factors associated with mortality at 28 days were asthma, cirrhosis, APACHEII score ≥ 28, and a dosage of sulbactam of 9 g/day for mortality at any timepoint. Treatment with colistin combined with sulbactam at 12 g/day was not superior to the combination treatment with sulbactam at 9 g/day. However, due to being an interim analysis, this trial was underpowered to detect mortality differences.

Summary: Background: Dengue is a common cause of acute liver failure in tropical countries. Paracetamol is the recommended antipyretic for dengue. Related observational studies in dengue have suggested that excessive paracetamol intake is related to hepatic injury. We aimed to evaluate whether standard dose paracetamol as an antipyretic in dengue infection caused transaminase elevation, and to evaluate the efficacy of paracetamol. Methods: In this randomised, double-blind, placebo-controlled trial, adult participants (aged ≥18 years) with dengue, as confirmed by either positive NS1 antigen, positive dengue IgM antigen with thrombocytopenia, or positive PCR test, were enrolled at three Royal Thai Army hospitals in Thailand. Key exclusion criteria were baseline AST or ALT concentrations of more than 3 times the upper limit of normal, cirrhosis, indication of paracetamol other than dengue infection, concurrent diagnosis of other causes of fever, or pregnancy. Patients were randomly assigned (1:1), by a computer-generated block randomisation procedure (block size of six), to receive either paracetamol (500 mg) or placebo (500 mg) every 4 h when body temperature exceeded 38°C during hospitalisation. Participants and investigators were masked to treatment assignment. The primary outcome was the proportion of participants with transaminase elevation, defined as serum aspartate transaminase (AST) and alanine transaminase (ALT) concentrations of more than 3 times the upper limit of normal on recovery day, in the intention-to-treat population. Prespecified interim analyses for safety and efficacy were performed with group sequential stopping boundaries. This trial is registered with ClinicalTrials.gov, number NCT02833584. Findings: Between Sept 1, 2016, and Dec 12, 2017, 125 participants were randomly assigned to receive either paracetamol (n=63) or placebo (n=62). 123 participants were included in the intention-to-treat population. The median daily dose of study medication was 1·5 g (IQR 0·8–2·0). The study was terminated early owing to a higher rate of transaminase elevation in the paracetamol group than in the placebo group (22% vs 10%; incidence rate ratio 3·77, 95% CI 1·36–10·46, p=0·011). The change of AST and ALT concentrations in the paracetamol group was higher than in the placebo group (mean difference 12·43 U/L per day, 7·16–17·71, p

The paper shows the research results related to the development of methods to increase the yield of spring wheat using Megamix liquid mineral fertilizers in the presowing treatment of seeds, treatment of crops on vegetation when introducing mineral fertilizers in seedbed preparation in the forest-steppe conditions of the Middle Volga region. The studies were carried out on the experimental field of Samara State University in 2017-2020. During the three-factor field experiment, dry matter accumulation and photosynthetic activity were evaluated with the analysis of photosynthetic potential and net productivity of photosynthesis. It was established that the best indicators are formed on versions with the treatment of seeding material with Megamix Seeds or Megamix Profi agents with subsequent double treatment on vegetation with Megamix Profi in the amount of 0.5l/ha (in the tillering phase) + Megamix Nitrogen in the amount of 0.5l/ha (in the flag leaf phase) against the background of N32P32K32 fertilizer application. The application of Megamix agents in the system of seed treatment + treatment of crops with Megamix stimulating agents provides the maximum accumulation of dry matter in the version of Megamix Seeds treatment and the treatment of crops with a mixture of Megamix Profi + Megamix Nitrogen – 591.9 g/m on soft crops and 622.6 g/m2 – durum wheat against the background of N32P32K32 application. The maximum photosynthetic potential of 0.968…1.091 million m2/ha per day is formed in these versions, and, consequently, the maximum yields with values of 3.73 t/ha on soft wheat crops and 3.44 t/ha on durum wheat crops. It was found that the use of liquid mineral fertilizers on all versions of the experiment reliably increases the yield of spring wheat.

The Middle Volga forest-steppe was subject to a comparative assessment to evaluate the effectiveness of combined insect-fungicidal pesticides as regulators of a phytosanitary state of farming ecosystems and yields of winter wheat. Insect-fungicidal pesticides used for pre-sowing treatment do not guarantee unconditional success, but they help to significantly reduce pest-induced losses and obtain safer grain produce. Regulated seeding rates showed that, once applied, combined dressing agents become slightly less biologically effective with overcrowding or thinning of crops. Dividend Supreme effectively reduced damage to shoots by Swedish flies, slightly worse than Celest Top. Celest Top and Dividend Supreme ensured stable suppression of root rot during the years of research. The winter wheat increasingly lodged when Celest Top and Dividend Supreme were used for seed dressing compared to the control (without dressing). Insect-fungicidal dressing agents increased the yield of winter wheat compared to the control and, at the same time, the risk of lodging. This effect was especially noticeable when Celest Top was used. It is recommended to use the combined Dividend Supreme and Celest Top pesticides for ensuring a stable phytosanitary situation and obtaining a high-quality harvest with a seeding rate of the target crop of 2-3 million seeds per 1 ha.

The methods of increasing productivity of sunflower hybrids using fertilizers and a micronutrient mixture Agromineral in the forest-steppe of the Middle Volga were described. The results of 2017–2018 studies are presented. The leaf area, the photosynthetic potential, the crop structure and the yield at different doses of fertilizers were assessed. The maximum value of the photosynthetic potential is formed by crops of the mid-season hybrid 8H477KLDM (4.386 million m2/ha per day). The use of fertilizers and micronutrient mixtures increases the photosynthetic potential and productivity by 9.09 ... 9.36 c/ha with an absolute value of 29.46 ... 31.83 c/ha.

The research was carried out in order to increase the productivity of oilseed flax and spring rape in Northern Kazakhstan. Experimental studies were conducted from 2012 to 2014 in Kostanay research Institute of agriculture (Republic of Kazakhstan). The experiment studied the sowing of flax and spring rape – 2nd decade of May; 3rd decade of May; 1st decade of June and the seeding rate for flax is 6.5; 7.0 and 7.5 million viable seeds/ha for spring rape – 2, 0; 2.5 and 3.0 million viable seeds/ha. During the years of research, the best coefficient of water consumption of the studied crops showed the second sowing period the third decade of May. According to the seeding standards, the formation of an optimal stem density increased the efficiency of moisture use. It was noted that moisture was most rationally consumed when sowing oilseed flax with a norm of 7.0 million sunflower seeds/ha (16.5-17.7 mm/c), spring rapeseed with a seeding rate of 2.5 million sunflower seeds/ha (9.9-11.2 mm/c). Oilseed flax sowing in the 3rd decade of May with a seeding rate of 7.0 million seeds/ha allowed to obtain the highest indicators of plant productivity in the experiments: yield is 13.1 c/ha, oil yield is 5.4 c/ha. In spring rape, the optimal sowing period was also the third decade of May; according to the seeding rate, the variant of 2.5 million suns excelled. seeds/ha sown in a given period: yield is 22.9 c/ha, oil collection is from 1 ha 9.4 c.

The article presents the results of scientific research on the growth-stimulating preparations in the pre-sowing treatment of soybean seeds and crops according to the development phases in the foreststeppe zone of the Middle Volga. It contains the results of the 2016-2018 research with an assessment of indicators of plant safety, photosynthetic activity and soybean yield in different treatment options by growth factors. The two-component preparations in pre-sowing seed treatment contribute to better soybean germination up to 78.12%. The pre-sowing treatment of seeds with Risotorphine and Raykat Start preparations forms the maximum leaf area. Comparing three years, we can say that the leaves work more productively in the variants with the use of Risotorphine and Raykat Start in pre-sowing treatment. Weather conditions in 2018 allowed soybean crops to form a high yield. The yield level was in the range of 1.48 - 1.98 t / ha. Inoculation of seeds with Raykat Start followed by crops treatment in the phase of 3-5 leaves and budding allowed achieving maximum yield for all years of research. After treating the seeds with Raykat Start, the maximum grain yield was 1.40 t/ha with a double-treatment of crops by microfertilizing mixture Megamix Profi in a phase of 3-5 leaves and budding.

Betulin-3,28-diphosphate (BDP) obtained by phosphorylation of betulin using POCl₃ has two main structural forms-BDP-1 and BDP-2-which differ in ethanol solubility, melting point, FTIR spectra, thermoanalytical characteristics and biological activity. Betulin-3,28-diphosphate and its sodium salt (Na-BDP) were characterized using 13 C and 31 P-NMR spectra, powder XRD experiments, as well as differential scanning calorimetry (DSC) and thermogravimetric analysis (TG) methods. The exo-effects at 193 ± 8 °C for ethanol soluble BDP-1 samples (-19.7 ± 0.2 kJ∙mol -1 ) were about three times less than for ethanol insoluble BDP-2 samples f (-70.5 ± 0.7 kJ∙mol -1 ). The DSC curves of Na-BDP-1 and Na-BDP-2 characterized the endo-effects having a maximum at 95⁻112 °C. Water-soluble Na-BDP-1 was obtained as needle-like crystals, unlike poorly crystalline Na-BDP-2, whereas BDP-1 and BDP-2 aged with time and were isolated as amorphous substances. In vitro experiments on rats showed that compared to the control, Na-BDP-1 increased catalase and SOD activity and improved energy metabolism more effectively than Na-BDP-2., Competing Interests: The authors declare no conflict of interest.

Background: The topical problems in balneotherapeutics and health resort activities in general are the development of the yellow clay-based preparations enriched in the natural mineral bischofite and the investigation of their therapeutic effects with the purpose of improvement of their curative potential., Aim: The objective of the present study was to evaluate the effectiveness of the course of the experimental therapeutic applications of the yellow clay obtained by the open pit mining of its deposits located in the vicinity of Pyatigorsk and modified by the addition of bischofite., Material and Methods: The experiments were carried out with the use of 57 eugamic Wistar male rats with adjuvant arthritis. The yellow clay supplemented with bischofite in various concentrations was applied in 12 procedures each 15 minutes in duration every other or every two days beginning from the 38 th day of experimentally-induced arthritis. The animals were allocated to five groups as follows: group 1 included the healthy animals that served as controls (n=5), groups 2-5 were comprised of the animals with adjuvant arthritis. The animals included in group 2 served as the experimental model of adjuvant arthritis (n=8), those comprising group 3 were treated by the applications of yellow clay without additives (n=14), group 4 was composed of the animals with adjuvant arthritis treated by the applications of yellow clay containing 10% of bischofite (n=15), the animals in group 5 having adjuvant arthritis were treated by the applications of yellow clay containing 20% of bischofite (n=15)., Results: The study has demonstrated the reduction of the reactively enhanced relative abundance of, activated T-cells, and B-lymphocytes down to the respective control values in the animals with adjuvant arthritis after the course of applications of the yellow clay preparations. Simultaneously, normalization of the immunoregulatory index, IRI, (the T-helpers to cytotoxic T-lymphocytes ratio) was documented. The treatment was associated with the strong dependence of the interleukin (IL-1β) contents on the cortisol level and the well apparent relationship between the levels of interleukins and IRI. Specifically, the relation between IL-1β and IRI following the application of non-modified yellow clay was characterized as (r=+0.8, p=0.03) in comparison with the relation between IL 6 and IRI (r=+0.8, p=0.03) after the treatment with yellow clay containing 10% of bischofite or between IL 6 and IRI (r=+0.8, p=0.004) after the application of yellow clay containing 20% of bischofite., Conclusion: The results of the study give evidence of the immunomodulatory action of yellow clay modified by the addition of bischofite. They suggest the promising opportunities for the application of these preparations for the management and rehabilitation of the patients presenting with the diseases of the musculoskeletal system in the future.

Seasonal and highly infectious strains of the influenza A and influenza B viruses cause millions of cases of severe complications in elderly people, children, and patients with immune diseases each year. Immunoglobulin A (IgA), which is an active component of humoral immunity, can prevent the spread of the virus in the upper respiratory tract. The preparation and study of the properties of recombinant virus-specific IgA could be an important approach to finding new means of preventing and treating influenza. Based on CHO DG44 cells, we developed stable monoclonal cell lines that produce monomeric and dimeric antibodies FI6-IgA1 and FI6-IgA2m1 to hemagglutinin (HA) of the influenza A virus. When studying the productivity, growth, and stability of the obtained clones, we found that the dimeric form of antibodies of IgA1 isotype is superior to other forms. The dimeric form of IgA antibodies plays a key role in mucosal immunity. Recognizing the prospects of using dimeric IgA as prophylactic and therapeutic mucosal drugs for viral infections, we studied their virus-neutralizing and antiviral activities on MDCK cell culture and compared them with the antibodies of the IgG1 isotype. This study presents the data on antiviral and virus-neutralizing activities of the FI6-IgA1 dimers to seasonal and highly infectious strains of influenza A virus.

Aim: The objective of the present study was to estimate the effectiveness of the new therapeutic modalities for the spa and health resort-based treatment of metabolic syndrome based on the results of the long-term follow-up observations., Material and Methods: A total of 100 patients presenting with metabolic syndrome were recruited for the participation in the study. All of them underwent a shortened course of mineral water intake in the combination with the use of the herbal medicinal products., Results: The results of the study give evidence of the more favorable changes in the clinical and instrumental characteristics of the patients with metabolic syndrome treated with the use of the proposed approach in comparison the patients treated by the conventional methods. Moreover, the beneficial effects of the proposed approach persisted during a longer period. The basal treatment given to our patients was supplemented by dietary therapy, therapeutic physical exercise, narzan baths, intake of mineral water having a temperature of 35-37 °С in conjunction with sulphate mineral water (narzan) cooled to 13-15 °С, and a phytococktail., Conclusion: The results of the long-term observations confirmed the enhanced effectiveness of the spa and health resort-based treatment of metabolic syndrome including the therapeutic courses with the intake of cooled narzan mineral water in the combination with phytococktails. This therapeutic modality increased the duration of the favorable changes of various parameters that characterize metabolic syndrome. Specifically, they persisted during 5-6 months after the application of the standard methods, were still apparent within 6-7 months after the two-week course of the treatment with cold narzan and phytococktails, and during 8-9 months when the duration of the treatment course was extended up to 3 weeks.

The title compound, C(13)H(13)NO(4)S, is a racemic mixture of enanti-omers. Short intra-molecular contacts between sulfonyl O and ester carbonyl C atoms are observed [C⋯O = 2.881 (1), 2.882 (1) and 2.686 (1) Å], indicating the possibility of donor-acceptor inter-actions between these groups. The dihedral angle between the phenyl and cyclopropyl rings is 79.3 (1)°.

The authors analyze rare lung diseases and describe a clinicomorphological case of bronioloalveolar carcinoma of the lung as one of rare bronchopulmonary diseases. According to the WHO histological classification (1999), the tumor is adenocarcinoma that is represented solely by bronchioloalveolar vegetations as a monolayer of the cells lining the walls of pre-existing alveoles without invasion of the stroma, vessels, and pleura. In 1876 Mallaser first described this rare disease in cloven-hoofed animals (Artiodactyla) in Scandinavian countries. Subsequently cases of this disease were also described in human beings.

The authors describe a rare case of undiagnosed lifetime malformation of the esophagus as its idiopathic enlargement undiagnosed in a 68-year-old male. The size of the organ was 10 to 20 cm in diameter and up to 25 cm in length. The esophageal mucosa was covered with the papillomatously changed laminated squamous epithelium with chronic inflammation in the mucous stroma. The case is of certain clinical and pathomorphological interest due to its rarity of undiagnosed lifetime malformation.

A rather rare case of melanoma with a rare primary localization in the pia mater is described. The available literature describes as many as 60 cases of melanomatosis at this site. This case is of certain clinical and morphological interest due to its rare localization and great clinical diagnostic difficulties.

A rare case of aspergillesis sepsis in an one month old baby with inborn leukemia is reported. Of essential importance in the pathology is genetic deficiency of this child, decreased immunity and a grave intoxication due to leukemia chemotherapy.

We studied the effect of cardiovascular system function on the response to terrain cure in the course of rehabilitation of 88 patients after surgical correction of valvular defects in conditions of low-mountain health resort. We have found that the response to the above exercise depends on functional condition of the cardiovascular system (the degree of correction of hemodynamic disorders related to valvular disease, the degree of myocardial hypertrophy and dilation of the chambers, left ventricular contractility). Terrain cure exercise promotes improvement in regulation of cardiovascular system and mobilization of its reserves.

80 Wistar male rats were kept for 24 days in moderate altitude conditions of mountain resort Teberda. Before the experiment and after it their blood was examined with enzyme immunoassay for hydrocortisone, T3, T4, TSH, with radioimmunoassay for insulin; glucose levels, dynamics of peripheral blood count, immune status were also measured. It was found that UV radiation has a negative effect on hormonal and immune status of healthy rats in medium-high mountains (hydrocortisone levels fell by 50%, insulin rose 5-6-fold, CIC rose by 24.2%, eosinophils count rose 3-fold, T-cell immunity and lymphocyte phagocyting activity got suppressed, lymphocyte/neutrophil proportion reduced by 35%. Intake of mineral water corrected all the negative effects of insolation but hyperinsulinemia decreased insignificantly.

Acute action of hypoxia was modelled by raising 26 Wistar male rats (body mass 230-250 g) in the low-pressure chamber at the height of 9000 m with the speed 15 m/s. The exposure was 60 min. Before and after lifting the rat blood was examined for contents of hormones, glucose and body temperature. It was found that hormonal reactions in maximal hypoxia and in drinking mineral water were virtually the same. This explains potentiation of hypoxia by mineral water. It is suggested that hypoxia and drinking mineral waters should be included in the complex strengthening the reserves of human body.

Hormonal status was examined in 30 intact male Wistar rats (body mass 200-220 g) and 10 healthy male volunteers aged 25-35 years. Hormonal status and influence of exercise were assessed in human males after 2, 10 and 19 days of stay in the sanatorium situated 2000 m above the sea level. The animals were decapitated on day 24 of their stay in the mountains. Blood from the rats' cervical vessels was examined for glucose, beta-lipoproteins, triiodothyronine, thyroxine, TTH, hydrocortisone. The findings indicate that stay in conditions of medium-height mountains climate aroused adaptation reactions in the hormonal systems, i.e. activation of thyroid hormones. An additional course of mineral water contributed to further rise of the blood hormones. Hormonal trends in the volunteers were similar. There was also a rise in the levels of beta-lipoproteins which was arrested by physical exercise.

284 patients with IHD after coronary artery bypass operation have undergone rehabilitation at low-mountain health resort Kislovodsk. The study of lipoprotein metabolism has detected a positive trend in this metabolism as shown by lowering of blood cholesterol, low density lipoproteins, phospholipids and triglycerides, elevated levels of high density lipoproteins.

Mechanical rectal injuries are severe traumas of the gastrointestinal tract which often cause fatal complications. The etiology of injuries to the rectum is diverse. They are inflicted with knives, occur in blunt injury of the abdomen, in injury with foreign objects, in falling from a height on a sharp object. Particularly important are traumas occurring during medical manipulations: in giving an enema, during rectosigmoidoscopy and colonoscopy, in electrocoagulation of polyps. Various methods are applied for the treatment of rectal injuries in intra- and extraperitoneal traumas, and an individual approach is needed in each case.

A rare case of an atypical course of hemochromatosis in a woman at the age of 25 years is described; it was characterized by predominant lesions of the cardiac muscle, liver, pancreas, by phenomena of cardiovascular incompetence, by the absence of signs of melanodermia.