Carriage of Neisseria meningitidis in newly enlisted young military professionals during the COVID-19 pandemic

Aim: Invasive meningococcal disease (IMD) is still a major threat not only to the youngest age group of children but also to adolescents and young adults. Higher rates of meningococcal disease have also been reported in specific at-risk groups, such as secondary and tertiary students and members of the military. Infection occurs after close contact with a clinically ill individual, but most often with an asymptomatic carrier. The aim of our study was to determine the prevalence of carriage of N. meningitidis in young persons newly enlisted in the Army of the Czech Republic (ACR). Material and methods: During August 2021, persons entering the service in the ACR were asked to participate in the presented study approved by the Ethics Committee. Nasopharyngeal and oropharyngeal swabs were collected from the study participants in August. A questionnaire survey was administered to each of them after signing an informed consent form. The biological samples were cultured on the day of collection and analysed for N. meningitidis. In case of meningococcal detection, the serogroup of N. meningitidis was determined. For most of the study participants, swabs were repeated after 2-3 months, in October and November. Swabs were also collected from additional participants, namely students entering the first year of bachelor and master studies at a military college. Results: A total of 252 newly recruited young military professionals, 201 males and 51 females, were included in the study. Carriage of N. meningitidis was found in 13 study participants, i.e., 5.2 % of all tested subjects, with a predominance of positive findings in the summer period. All carriers were males while in females, meningococcal carriage was not detected. In carriers, serogroup B was predominant over non-groupable isolates (NG). There was no evidence of carriage of meningococcal groups A, C, W, X, or Y. Meningococcal isolation was significantly more successful from oropharyngeal compared to nasopharyngeal swabs. Only in five of 17 positive findings, meningococci were detected from both the oropharynx and nasopharynx. No isolation was made from the nasopharynx alone. Conclusion: The lower percentage of meningococcal carriage in young military professionals in the Czech Republic in the study period 2021 as compared to similar reports on military collectives from other countries can be attributed to the current epidemic situation, where the measures taken in connection with the efforts to prevent the spread of COVID-19 resulted in the loss of seasonality of respiratory diseases and also their significantly lower incidence. This correlates with a reduction in carriage in the monitored age category.

Differential diagnosis of ascites in internal medicine: clinical case.

Ascites and hydrothorax may be the symptoms of congestive heart failure and do not always reflects presense of the decompensated liver cirrhosis. Clinical examination of patient with chronic hepatitis C which cyanosis of the lips, cervival veins pulsation, a triple heart rhythm indicated on pathology of the heart (constrictive pericarditis), which was confirmed by instrumental methods. Congestive heart failure has lead to the congestive liver in a young female patient. Regression of all the symptoms of heart failure occurred after surgical treatment (pericardectomy).

Molecular genetic analysis in 14 Czech Kabuki syndrome patients is confirming the utility of phenotypic scoring.

Kabuki syndrome (KS) is a dominantly inherited disorder mainly due to de novo pathogenic variation in KMT2D or KDM6A genes. Initially, a representative cohort of 14 Czech cases with clinical features suggestive of KS was analyzed by experienced clinical geneticists in collaboration with other specialties, and observed disease features were evaluated according to the 'MLL2-Kabuki score' defined by Makrythanasis et al. Subsequently, the aforementioned genes were Sanger sequenced and copy number variation analysis was performed by MLPA, followed by genome-wide array CGH testing. Pathogenic variants in KMT2D resulting in protein truncation in 43% (6/14; of which 3 are novel) of all cases were detected, while analysis of KDM6A was negative. MLPA analysis was negative in all instances. One female patient bears a 6.6 Mb duplication of the Xp21.2-Xp21.3 region that is probably disease causing. Subjective KS phenotyping identified predictive clinical features associated with the presence of a pathogenic variant in KMT2D. We provide additional evidence that this scoring approach fosters prioritization of patients prior to KMT2D sequencing. We conclude that KMT2D sequencing followed by array CGH is a diagnostic strategy with the highest diagnostic yield.

[Myocardial Crypt of the Left Ventricle Combined With Barlows syndrome].

Myocardial crypts were initially described in patients with hypertrophic cardiomyopathy. Modern diagnostic data show that this structural abnormality can be found in patients with other diseases, or might represent the variant of normal heart development in healthy individuals. The prognostic significance of this finding is uncertain. In this publication we present a clinical case of the combination of myocardial crypt and Barlows syndrome.

[EXPERIMENTAL ASSESSMENT OF THE IMMUNOTROPIC EFFECTS OF ARABINOGALACTAN AND PECTINACEOUS POLYSACCHARIDES ISOLATED FROM FERULA KUCHISTANICA.]

It is established that arabinogalactan and pectinaceous polysaccharides isolated from Ferula kuchistanica are capable of stimulating a primary immune response in mice by increasing the number of antibody-producing cells in the spleen in response to immunization with sheep red blood cells in both intact animals (on average by 51.0%; p < 0.005) and those with secondary immunodeficiency caused by irradiation (on average by 164.4%; p < 0.005). The treatment with compounds studied also significantly increased the functional condition of cells of the mononuclear phagocyte system (on average by 27.0%; p < 0.005).

[Noncoronary dilated cardiomyopathy after reverse remodeling heart surgery].

We present here analysis of surgical treatment of 24 patients (5 women, 19 men, age 20-75, mean age 50.7 +/- 2.5 years) with dilated cardiomyopathy (DCM) operated during the period from 2008 to 2013. Duration of the disease ranged from 4 months to 12 years (mean 49.4 +/- 7.5 months). According to symptoms and results of 6-minute walk test 3 patients (13%) had heart failure NYHA class III and 21 patients (87%)--NYHA class IV. Average end-diastolic left ventricular size was 7.4 +/- 0.18 cm (6.0-9.2 cm), ejection fraction--26.7 +/- 2.1% (13-47%), mean pulmonary artery pressure 54.9 +/- 2.9 mm Hg (35-80 mmHg). All patients underwent organ-conserving surgery aimed at reverse remodeling of the heart. Surgery was accompanied with implantation of implantable cardioverter defibrillator in 3 patients and/or cardiac resynchronization therapy device in 6 patients. Two patients (8.3%) died during hospitalization of hemodynamically significant ventricular arrhythmias; seven patients (29.2%) died in the late postoperative period. The results of the analysis indicate that reverse-remodeling surgery may be effective in patients with DCM of any age group with preserved reserves of the liver, kidney, and lung function in the absence of active myocarditis. Further observations are needed to determine the place of this operation in the protocol of treatment of patients with DCM.

[The mitral valve dysplasia in adults: the choice of surgical tactics].

Early and long-term results of hereditary mitral valve dysplasia surgical treatment were obtained in 203 patients. All patients were divided in 2 groups: 73 (36%) patients after valve-preserving operations and 130 patients after universal chorda-preserving valve prosthetics. The choice of treatment modality depended on the type of anatomical changes and overall surgical volume. Hospital lethality rate was 2.46%. Surgery led to satisfactory functional results, thus, 83.3% of the operated patients have I-II NYHA functional class. Analysis of the own experience allowed to mark out factors, contraindicating the durable plastic mitral valve.

[The donor's heart 22 years after the orthotopic transplantation].

The orthotopic heart transplantation is an acknowledge method for the treatment of cardiomyopathies of various etiology. Specific vasculopathy of the transplanted heart is considered to be a significant problem of the long-term postoperative period and serves the reason of low 10-years survival rates (not more then 50%). The issue unites the experience of follow-up and intravital electronic microscopy of transplantated heart's biopsies from 20 patients. Previously unknown data can help the clarification of posttransplantational cardiomyopathy.

Assessment of the Relationship Between Protocol Adherence, Study Complexity and Personnel in Surgical Clinical Trials.

BACKGROUND: In order to improve quality and efficiency of surgical trials, we assessed protocols complexity and examined whether it influenced the conduct, as measured by the number and types of deviations that occurred during the execution phase. Knowledge of these facts and performance of research team would allow to effectively mitigate the occurrence of deviations. METHODS: Thirty-five research protocols were rated according to a previously established complexity scoring model. Statistical analyses were performed to examine associations between protocol complexity, number of protocol/informed consent amendments vs. number/types of protocol deviations; as well as correlations with phase of the study, type of investigational product, personnel changes/experience level were assessed. RESULTS: Assessment of complexity score in Pearson's correlation test with the number of protocol deviations showed weak correlation, suggesting that other factors can influence protocol adherence. There was no correlation observed between number of deviations and type of study by investigational product category. In examining association between protocol deviations and number of subjects enrolled a trend was observed towards increased number of deviations once more subjects have entered the study. The higher number of protocol deviations was associated with increased number of protocol amendments (p = 0.0396), and there was no statistical significance observed between number of deviations and informed consent amendments (p = 0.5083). There was a moderate correlation detected between increased number of protocol deviations and total number of investigators on the study. CONCLUSION: Protocol adherence can be improved with effective training and retention of research coordinators, investigators and frequent internal auditing to address discrepancies and effectively implement corrective actions. Upfront training of research personnel, with subsequent monitoring of performance metrics throughout the execution phase can reduce the total number of protocol deviations, ensure data integrity and improve quality of research conducted. Engagement of all stakeholders upfront, including clinical site personnel, can help develop well-designed clinical trial protocol, avoid time consuming and costly protocol and informed consent amendments at execution phase and ensure higher quality of research conducted, while allowing to meet objectives of the trial in a more efficient manner.

Ectodermal dysplasia: important role of complex dental care in its interdisciplinary management.

AIM: Despite the fact that ectodermal dysplasia (ED) is a rare disease, it is often seen in a tertiary clinic. ED affects ectodermal tissues such as skin, hair, teeth, nails, and sweat glands. Patients usually have sparse light hair, deformed nails, and dry skin. They suffer from dental abnormalities such as oligodontia (absence of 6 or more teeth) or complete anodontia; salivation can also be affected. The absence of teeth can be the overriding problem for both patients and their parents, and lead to substantial social ostracisation. This study aims to summarise the facts about the disease, especially dental treatment options based on data drawn from a representative Czech cohort. MATERIALS: The present article summarises the facts about ectodermal dysplasia (ED) in a cohort of 13 patients, where the following were evaluated: clinical manifestations of ED, pathogenic variants detected in selected candidate genes and dental treatment options from child removable dentures to fixed crowns and implants insertion. Three cases are described in detail and demonstrate approaches for different age groups. CONCLUSION: Early diagnosis and active cooperation between the geneticist and dentist will facilitate cooperation with parents and patients and assure secondary prevention. It is preferable that the geneticist understands dental treatment options and can discuss these with patients/parents.

The structure and prebiotic activity of arabinogalactan from Ferula Kuhistаnica.

Acidic arabinogalactan with molecular weight 36 kDa was isolated from the aerial part of Ferula kuhistаnica, the monosaccharide composition of which is represented by galactose and arabinose in a ratio of 3.6:1. The chemical and spectral methods revealed a main polymer chain consisting of (1 â†’ 6) ß-galactopyranose residues, where in position of C-3 were the residues of α-arabinofuranose and its 1,5-linked oligomers, as well as ß-GlcpA-4-OMe-(1 â†’ 6)-ß-Galp-(1→ fragments. In addition, a small part of the main chain carries monosaccharide residues of ß-Galp-(1→ in position C-2. The effect of arabinogalactan on the growth of an associative culture of bifidobacteria and some mono-strains of lactobacilli was studied and it was shown that it exhibits more effective prebiotic activity.

Risk-Based Quality and Compliance Management in Clinical Trials with Combination Products in Changing Global Regulatory Environment.

BACKGROUND: Newly emerging products which combine drugs, devices, and biologics are expected to provide new opportunities in bridging device and drug capabilities and establish synergies while bringing sophisticated combination products to consumers. The emergence of these novel products has triggered new regulatory, strategic, and technological challenges. While progress has been made at clarifying the issues that arise most frequently, regulatory authorities and product developers continue to struggle with complex regulatory and technical issues encompassing the development programs for combination products. A risk-based approach requires not only a strategy but also tools to define key indicators to measure specific risks. Key risk indicators (KRIs) and risk-based quality management systems should focus on safety of research subjects and data integrity. METHODS: We analyzed current regulatory guidelines throughout the life cycle of combination products and compared old and new approaches to risk-based quality and compliance management for current good manufacturing practices and during pre-clinical and clinical phases of combination products development. Cause-effect analysis for two major risk categories in clinical trials with combination products was performed. RESULTS: The results of our analysis are based on observations from 15 clinical trials, which were conducted with combination products. Based on our findings, we proposed practical recommendations for the development of KRIs to improve conduct and ensure safety of research subjects in trials with combination products by utilizing risk-based quality management approach. CONCLUSION: Combination products, due to their specific nature, can increase risks while being tested in clinical trials. Metrics critical to risks and quality management should be linked to particular processes within development program for combination products. Ongoing collaboration between regulators, industry, and other stakeholders is essential to streamlining of the global combination entities development and approval process in a way that will produce safe and effective products for consumers.

Steroid diagnostics of 21st century in the light of their new roles and analytical tools.

The determination of steroid hormones and subsequent interpretation of results is accompanied by a range of difficulties. The amount of information that current technology can provide on the circulating concentrations of more than a hundred various steroid compounds can lead to problems with interpretation. The aim of this study is to help provide orientation in this maze of data on steroid hormones. First we focus on specific aspects arising from the pre-analytical phase of steroid determination that need to be considered when planning sampling, whether for diagnostics or research. Then, we provide a brief summary of the characteristics and diagnostic relevance of several steroid hormones and/or their metabolites: pregnenolone, 17alpha-hydroxy-pregnenolone, dehydroepiandrosterone, hydroxyderivatives of dehydroepiandrosterone, androstenedione, testosterone, estrone, estradiol, estriol, cortisol, cortisone, which in our institute are determined with validated LC-MS/MS methods. For these steroids, we also provide newly calculated reference values in fertile women according to the phase of their menstrual cycle.

[Aanalysis of resistance and its transferability in microflora from primary meat production]. / Analýza rezistence a její transferability u mikroflóry z prvovýroby masa.

Resistance spectra and their transferability were studied in G- strains isolated from the primary production of meat by the method after Bohus (1974). Out of the set of strains, 93% were resistant, and out of these, 65% were multiresistant. Thirty-five per cent of the resistant strains were R plasmid donors. Of the two recipients, the laboratory strain of E. coli IHE Nx was significantly better. Among the 21 determined resistance spectra, the following were the most frequent: Tc, SmTcSu, and TcAm. Transfer of two to four, or even six, different plasmid types, mostly simple, was recorded from the two most frequent complex types of donor strain resistance: SmCmTcAmSu and SmTcAmSu. The determinants Tc and Am prevailed in the spectra of the transferring R plasmids, mostly as separate markers and only in 21 to 36% of cases in more complex types.

[Chlortetracycline residues in the meat of slaughter calves in relation to transmissible microbial resistance to antibiotics]. / Rezidua chlortetracyklinu u jatecných telat ve vztahu k prenosné mikrobiální rezistenci na antibiotika.

The occurrence of chlortetracycline residues in the meat of slaughter calves in 62% herds under study (the additive of the medicated premix AUREOVIT to feed without observing the withdrawal times) did not influence significantly the Gram-negative resistant and R+ microflora isolated from the same material, in comparison with control herds that were administered no antibiotics. Neither was the spectrum of donors and transferring R plasmids influenced significantly nor the incidence of different resistance determinants. The effect of chlortetracycline addition to feed was negative (at P = 0.05) only in the occurrence of R+ microflora isolated from stable environment where the slaughtered calves had been housed.

[Persistance of penicillin residues in the calf organism after parenteral therapeutical administration of the preparation penicillin G, procaine inj ad usum vet]. / Pretrvávání reziduú penicilínu v organismu telat po parenterálnn lécebné aplikaci prípravku Prokain-penicilin G inj. ad usum vet

By means of two biological diffusion methods a penicillin content in various calf tissues was determined. For the injections PROKAIN Penicillin G Spofa, inj. adusum vet., was used in a single dose of 25 000 i. u. kg-1 body mass. For the tests three collection strains -- B. subtilis (ATCC 6633), Sarcina lutea (ATCC 9341), and Micrococcus flavus (ATCC 10240) were used. A quantitative determination of penicillin in the samples was accomplished by reading from the standard curves. Sensitivities of the two methods were approximately the same; Micrococcus flavus proved most suitable of the microorganisms employed. At 2, 3, 5 and 20 post-treatment days both test animals were positive; at 10 days three out of four calves examined were positive, whereas at 15 days two out of three calves examined were positive. The residues were most frequently found in the liver, kidney and at the injection sites. Maximum detectable concentrations were at the injections sites, minimum ones in the bone marrow. In the musculature (noninjection site) a small quantity of penicillin was found up to 20 days after the application. Current culinary and technological treatment of positive meat and liver samples did not always suffice for complete inactivation of the penicillin residues. For the tested preparation, a preslaughter withdrawal time of 30 days is recommended.

[Persistance of streptomycin residues in the calf organism after parenteral therapeutic administration]. / Pretrvávani reziduí streptomycinu v organismu telat po jeho parenterální lécebné aplikaci

Streptomycin concentrations were determined in various calf tissues after i. m. administration of Streptomycin sulphate preparation of Rumanian provenience in the dose of l g pro toto using the biological diffusion method according to Gartside (1960). Spore suspensions of B. subtilis (ATCC 6633) and B. cereus var. mycoides (ATCC 11778) strains were employed as test organisms. B. subtilis was able to reveal considerably more residues. Another method using vegetative forms of the above microorganisms proved unsuitable for the tests. Two, three, five and ten days after the injection both slaughtered calves were positive, at 15 days only one of the two calves examined was positive, whereas at 20 days both calves were negative. Of the individual samples predominant majority of the findings come from the liver and from the spot of injection; residue findings from other tissues (bile, peritoneal muscles) are only sporadic. Skeletal musculature was negative in all cases except for the site of injection. In the samples from the injection site antimicrobial resudue activity was demonstrated in two cases following 1 month of freezing at -15 to -20 degrees C. For the tested preparation, a preslaughter withdrawal time of 20 days is recommended.

[Residues of chloramphenicol in the calf organism following parenteral administration of the Czechoslovak preparation Chronicin inj]. / Rezidua chloramfenikolu v organismu telat po parenterální aplikaci cs. prípravku Chronicin inj

Using two biological methods the chloramphenicol content in various tissues of 11 calves aged 3--18 days was determined after a single-dose therapeutical administration of the Czechoslovak preparation of Chronicin inj. in the quantity of 12 mg kg-1 body mass. Of four test strains, solely Micrococcus flavus (ATCC 10240) strain proved suitable. Chloramphenicol was quantitatively determined by reading from transformed standard curves. An evalua tion of the two approximately equally sensitive methods yielded the following results: three days after the injection all calves were positive, at 5 and 10 days, one of three calves in each group was negativ similarly to both calves slaughtered 15 days post injection. The residues appeared most frequently in the liver, at the site of injection, and in the fore and hind musculature. Maximum detectable concentrations were recorded in the liver. Culinary and technological treatment of positive meat and liver samples revealed that 15 minutes' boiling and 30 minutes' roasting destroyed the microbiologically active chloramphenicol residues in the samples. Neither deep freezing nor salting was sufficient for residue inactivation, although in some samples a decrease in biological chloramphenicol activity by circa 20--30% was recorded. a preslaughter withdrawal time of 15 days is recommended.