Reconstructing the subcephalic musculature in Pucapampella and Ichthyostega.

We present new reconstructions of subcephalic musculature for the stem chondrichthyan Pucapampella, the tetrapodomorph fish Eusthenopteron, and the Devonian tetrapod Ichthyostega. These reconstructions are based on macroscopic dissections of the head muscles of an archaic shark Heptranchias and an archaic actinopterygian Polypterus, that are combined with functional considerations and a reappraisal of not widely known theoretical concepts from the past. The subcephalic, as well as the supracephalic, musculature is formed by four anterior myomeres. They are continuous with subsequent myomeres of the trunk, but are innervated by ventral nerve roots of the medulla oblongata and thus belong to the head. The fourth subcephalic myomere ends with its posterior myoseptum on the occiput in osteichthyans, but on the first vertebra in chondrichthyans. The original function of subcephalic and supracephalic muscles in basal gnathostomes supposedly was to hold together anterior and posterior parts of the neurocranium during interaction with prey, such as the backward-ripping prey dissection, hypothesized for Pucapampella. In sarcopterygian osteichthyans, subcephalic musculature is involved in active depression of the anterior part of the neurocranium; specialization of this mechanism resulted in a complete separation of m. subcephalicus from trunk myomeres in Latimeria. Fusion of anterior and posterior parts of the neurocranium has resulted in reduction of the subcephalic musculature in the majority of cartilaginous and bony fishes. However, hexanchid sharks retain three posterior subcephalic myomeres for backward-ripping prey dissection. Polypterus and Chauliodus have retained the subcephalic musculature, but its function has shifted to a depression of the whole neurocranium.

Changes in nasal, pharyngeal and salivary secretory IgA levels in patients with COVID-19 and the possibility of correction of their secretion using combined intranasal and oral administration of a pharmaceutical containing antigens of opportunistic microorganisms.

Background: Although extensive research has been conducted on the role of local immunity in patients with SARS-CoV-2, little is known about the production and concentrations of secretory IgA (SIgA) in different mucosal compartments. This article aims to assess the secretion of SIgA in the nasal and pharyngeal compartments and saliva of patients with COVID-19 and to investigate the possibility and efficiency of correction of their secretion using combined intranasal and oral administration of a pharmaceutical containing antigens of opportunistic microorganisms. Methods: This study included 78 inpatients, aged between 18 and 60 years, who had confirmed COVID-19 with moderate lung involvement. The control group (n=45) received basic therapy, and the treatment group (n=33) was additionally administered the bacteria-based pharmaceutical Immunovac VP4 from day 1 to day 10 of hospitalization. SIgA levels were measured by ELISA at baseline and on days 14 and 30. Results: No systemic or local reactions associated with Immunovac VP4 were reported. We observed a statistically significant reduction in the duration of fever and hospitalization in patients who received Immunovac VP4 compared with those from the control group (p=0.03 and p=0.05, respectively). Changes over time in SIgA levels in nasal swabs were found to be significantly different in the two treatment groups (F=7.9, p[78.0]<0.001). On day 14 of observation, patients in the control group showed a statistically significant reduction in SIgA levels from baseline (p=0.02), whereas patients in the Immunovac VP4 group had stable SIgA levels (p=0.07). On day 30 after the start of treatment, there was a statistically significant increase in SIgA levels in the Immunovac VP4 group compared with baseline (from 77.7 (40.5-98.7) µg/L to 113.4 (39.8-156.7) µg/L; p=0.05) and the levels measured on day 14 (from 60.2 (23.3-102.9) µg/L to 113.4 (39.8-156.7) µg/L; p=0.03). The control group showed a statistically significant decrease in levels of nasal SIgA (to 37.3) on day 30 (p=0.007 for comparison with baseline values and p=0.04 for comparison with levels measured on day 14). Changes over time in SIgA levels measured in pharyngeal swabs were also different between the two treatment groups, and this difference reached statistical significance (F=6.5, p[73.0]=0.003). In the control group, this parameter did not change throughout the study (p=0.17 for a comparison between the levels measured on day 14 and the baseline values, and p=0.12 for a comparison between the levels measured on day 30 and the baseline values). In the Immunovac VP4 group, there was a statistically significant increase from baseline in SIgA levels on study day 30: from 1.5 (0.2-16.5) µg/L to 29.8 (3.6-106.8) µg/L (p=0.02). Changes over time in salivary SIgA did not show a significant difference between study groups (F=0.3, p[66.3]=0.75). Conclusion: As part of combination therapy, the bacteria-based immunostimulant agent Immunovac VP4 increases SIgA levels in the nasal and pharyngeal compartments and induces clinical improvement. Induced mucosal immunity is central to the prevention of respiratory infections, particularly in patients with post-COVID-19 syndrome.

Mucosal immunity in health care workers' respiratory tracts in the post-COVID-19 period.

Coronavirus disease (COVID-19) has generated interest in the assessment of systemic immune status, but existing knowledge about mucosal immunity is clearly insufficient to understand the full pathogenetic mechanisms of the disease. The aim of this study was to evaluate the long-term effects of novel coronavirus infection on mucosal immunity in the postinfection period among health care workers (HCWs). A total of 180 health care workers with and without a history of COVID-19 who ranged in age from 18 to 65 years were enrolled in this one-stage, cross-sectional study. The study subjects completed the 36-Item Short Form (36) Health Survey (SF-36) and the Fatigue Assessment Scale. Secretory immunoglobulin A (sIgA) and total immunoglobulin G (IgG) levels were quantified in saliva samples, induced sputum samples, and nasopharyngeal and oropharyngeal scrapings by an enzyme-linked immunosorbent assay. Specific anti-SARS-CoV-2 IgG antibodies were quantified in serum samples by chemiluminescence immunoassay. Analysis of the questionnaire data showed that all HCWs with a history of COVID-19 reported health problems that limited their daily activities and negative changes in their emotional health three months after the disease, regardless of its severity. The following shifts were detected in the adaptive arm of the immune response in different mucosal compartments. Among subjects who had severe or moderate-to-severe COVID-19, salivary sIgA levels were significantly higher than those in the control group (p < 0.05 and p < 0.005, respectively). Compared to the subjects in the control group, all subjects with prior COVID-19 had significantly higher levels of total IgG in induced sputum. In the group of patients who had had severe infection, total IgG in saliva was also higher (p < 0.05). A direct statistically significant correlation was also detected between the levels of total IgG in all studied samples and the levels of specific IgG antibodies against SARS-CoV-2 in the serum. A significant correlation was observed between total IgG levels and the parameters of physical and social activities, mental health, and fatigue levels. Our study demonstrated long-term changes in the humoral mucosal immune response, which were most pronounced in health care workers with a history of severe or moderate-to-severe COVID-19, and an association of these changes with certain clinical signs of post-COVID-19 syndrome.

Application of vibrational spectroscopy and nuclear magnetic resonance methods for drugs pharmacokinetics research.

OBJECTIVES: The development of new methods for determining the concentration of drugs is an actual topic today. The article contains a detailed review on vibrational spectroscopy and nuclear magnetic resonance methods using for pharmacokinetic research. This study is devoted to the possibility of using vibrational spectroscopy and 1H nuclear magnetic resonance spectroscopy to determine the concentration of drugs and the use of these groups of techniques for therapeutic drug monitoring. CONTENT: The study was conducted by using scientific libraries (Scopus, Web of Science Core Collection, Medline, GoogleScholar, eLIBRARY, PubMed) and reference literature. A search was conducted for the period from 2011 to 2021 in Russian and English, by combinations of words: 1H nuclear magnetic resonance (1H NMR), vibrational spectroscopy, Surface-Enhanced Raman spectroscopy, drug concentration, therapeutic drug monitoring. These methods have a number of advantages and are devoid of some of the disadvantages of classical therapeutic drug monitoring (TDM) methods - high performance liquid chromatography and mass spectrometry. This review considers the possibility of using the methods of surface-enhanced Raman scattering (SERS) and 1H NMR-spectroscopy to assess the concentration of drugs in various biological media (blood, urine), as well as to study intracellular metabolism and the metabolism of ophthalmic drugs. 1Н NMR-spectroscopy can be chosen as a TDM method, since it allows analyzing the structure and identifying metabolites of various drugs. 1Н NMR-based metabolomics can provide information on the side effects of drugs, predict response to treatment, and provide key information on the mechanisms of action of known and new drug compounds. SUMMARY AND OUTLOOK: SERS and 1Н NMR-spectroscopy have great potential for further study and the possibility of introducing them into clinical practice, including for evaluating the efficacy and safety of drugs.

Suboccipital muscle of sharpnose sevengill shark Heptranchias perlo and its possible role in prey dissection.

Skull and head muscles of Heptranchias perlo were studied. Its distinctive features include the suboccipital muscles, described for the first time, the absence of the palatoquadrate symphysis, a longitudinally extended mouth, and teeth unsuited for dissecting prey in typical method of modern sharks, which is cutting motions powered by head shaking from side to side. The palatoquadrate cartilages of H. perlo and closely related Hexanchidae articulate with the neurocranium via orbital and postorbital articulations, which together allow for lateral expansion of the jaws, but restrict retraction and protraction. We interpret these features as an adaptation to a different method of prey dissection, that is, ripping in a backward pull. It employs the specific postorbital articulation together with the suboccipital muscles as force-transmitting devices, and is powered by swimming muscles which produce a rearward thrust of the tail. During this type of dissection, the anterior part of the vertebral column should experience a tensile stress which explains the replacement of rigid vertebral bodies by a collagenous sheath around the notochord in H. perlo. The backward-ripping dissection could have been common among ancient Elasmobranchii based on the similarly developed postorbital articulation, a longitudinally extended mouth, and the absence of the palatoquadrate symphysis. A biomechanical comparison with the extinct Pucapampella indicates that ancient elasmobranchs could be also specialized in the backward-ripping prey dissection, but their mechanism was different from that inferred for H. perlo. We suggest that in the early evolution of sharks this mechanism was replaced by head-shaking dissection and then later was restored in H. perlo on a new morphological basis. A new position of the postorbital articulation below the vertebral axis is fraught with the braincase elevation when backward ripping the prey, and as a counter-mean, requires formation of suboccipital portions of the axial musculature unknown in other sharks. Homology and origin of these portions is considered.

Functional analysis of the musculo-skeletal system of the gill apparatus in Heptranchias perlo (Chondrichthyes: Hexanchidae).

Musculo-skeletal morphology is an indispensable source for understanding functional adaptations. Analysis of morphology of the branchial apparatus of Hexanchiform sharks can provide insight into aspects of their respiration that are difficult to observe directly. In this study, I compare the structure of the musculo-skeletal system of the gill apparatus of Heptranchias perlo and Squalus acanthias in respect to their adaptation for one of two respiratory mechanisms known in sharks, namely, the active two-pump (oropharyngeal and parabranchial) ventilation and the ram-jet ventilation. In both species, the oropharyngeal pump possesses two sets of muscles, one for compression and the other for expansion. The parabranchial pump only has constrictors. Expansion of this pump occurs only due to passive elastic recoil of the extrabranchial cartilages. In Squalus acanthias the parabranchial chambers are large and equipped by powerful superficial constrictors. These muscles and the outer walls of the parabranchial chambers are much reduced in Heptranchias perlo, and thus it likely cannot use this pump. However, this reduction allows for vertical elongation of outer gill slits which, along with greater number of gill pouches, likely decreases branchial resistance and, at the same time, increases the gill surface area, and can be regarded as an adaptation for ram ventilation at lower speeds.