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OBJECTIVE To determine the pharmacokinetics and pharmacodynamics of dexmedetomidine after IM administration in dogs. ANIMALS 6 healthy adult purpose-bred dogs (3 males, 3 females) with a mean ± SD body weight of 25.2 ± 1.8 kg. PROCEDURES Each dog received 10 µg/kg dexmedetomidine, IM. Heart rate and respiratory rate were counted via cardiac auscultation and visual assessment of chest excursions. Sedation was assessed utilizing 2 sedation scoring systems. Plasma concentrations were determined using ultra performance liquid chromatography–mass spectrometry. Plasma concentrations versus time data after IM dexmedetomidine were analyzed using noncompartmental analysis for extravascular administration. RESULTS Over the first 2 hours following IM injection of dexmedetomidine, plasma concentrations fluctuated in each dog. The geometric mean (range) maximum plasma concentration was 109.2 (22.4 to 211.5) ng/mL occurring at 20.5 (5 to 75) minutes, and the mean half-life was 25.5 (11.5 to 41.5) minutes. Heart rate was significantly lower than baseline from 30 minutes to 2 hours postdexmedetomidine administration, and respiratory rate was significantly lower than baseline from 45 minutes to 1.75 hours. Dogs were significantly more sedated from 30 minutes to 1.5 hours postdexmedetomidine administration. Median time to onset of sedation was 7.5 minutes (range, 2 to 10 minutes), and median time to peak sedation was 30 minutes (range, 15 to 60 minutes). CLINICAL RELEVANCE Variations in plasma concentrations occurred in all dogs for the 2 hours postinjection of dexmedetomidine at 10 µg/kg, IM. This was likely due to alterations in absorption due to dexmedetomidine-induced local vasoconstriction. Despite variable plasma concentrations, all dogs were sedated following IM dexmedetomidine administration.

In this study, we report the potential of 2D/2D TiO2-GO-ZnFe2O4 photocatalyst obtained using the fluorine-free lyophilization technique for the degradation of ibuprofen belonging to the group of active pharmaceutical ingredients (API). The improved ibuprofen degradation under simulated solar light was achieved in the presence of a composite of 2D TiO2 combined with GO and embedded ZnFe2O4, which additionally provides superparamagnetic properties and enables photocatalyst separation after the photodegradation process. After only 20 min of the photodegradation process in the presence of 2D/2D TiO2-GO-ZnFe2O4 composite, more than 90% of ibuprofen was degraded under simulated solar light, leading to non-toxic and more susceptible to biodegradation intermediates. At the same time, photolysis of ibuprofen led to the formation of more toxic intermediates. Furthermore, based on the photocatalytic degradation analysis, the degradation by-products and possible photodegradation pathways of ibuprofen were investigated. The photodegradation tests and electronic spin resonance analyses indicated the significant involvement of superoxide radicals and singlet oxygen in the ibuprofen photodegradation process.

Contact tracing is an important intervention measure to control infectious diseases. We present a new approach that borrows the edge dynamics idea from network models to track contacts included in a compartmental SIR model for an epidemic spreading in a randomly mixed population. Unlike network models, our approach does not require statistical information of the contact network, data that are usually not readily available. The model resulting from this new approach allows us to study the effect of contact tracing and isolation of diagnosed patients on the control reproduction number and number of infected individuals. We estimate the effects of tracing coverage and capacity on the effectiveness of contact tracing. Our approach can be extended to more realistic models that incorporate latent and asymptomatic compartments.

Aim of the study: To compare the serum levels of IL-12 and IL-23 between healthy volunteers and patients with multiple sclerosis with regard to their cognitive function. Materials and methods: A total of 21 patients with multiple sclerosis and 21 healthy individuals were enrolled into the study. The individuals were age- and sex-matched. Each participant was evaluated using the Montreal Cognitive Assessment (MoCA), the Beck Depression Inventory (BDI), and the Pittsburgh Sleep Quality Index (PSQI). The enzyme-linked immunosorbent assay was performed to assess the serum levels of IL-12 and IL-23. Results: The concentration of IL-12 was 1.61 ± 4.61 pg/mL in the group of patients with multiple sclerosis and 1.78 ± 3.54 pg/mL in the control group, p = 0.5009. The concentration of IL-23 was 19.04 ± 75.50 pg/mL in the study group and 5.50 ± 14.4 pg/mL in the control group, p = 0.5170. A significant difference was found between the control and study groups in the MoCA cognitive test (28 vs. 24 points, respectively, p < 0.0001). There was no significant difference in the Beck Depression Inventory and PSQI between the control and study groups. No significant correlations were found between the IL-12/IL-23 serum levels and psychological evaluations. Conclusions and clinical implications: The results obtained indicate that IL-12 and IL-23 may not play a role in the development of cognitive impairment. The assessment of cognitive impairment in patients with multiple sclerosis may have a screening value in preventing their cognitive deterioration.

Nanocrystalline powders of LiCoO2 were synthesized using a modified solution combustion method, and the effects of the annealing temperature (450–900 °C) on structure and composition were investigated using various methods, including XRD, SEM, EPR, and electrical studies. It was found that, as the process temperature increases, the value of the specific surface area decreases, and, hence, the size of the crystallites increases. XRD analysis showed that phase-pure LiCoO2 material was maintained without additional phases. EPR studies revealed the presence of two Ni3+ complexes resulting from Ni impurities. The electrical properties of the studied LiCoO2 samples were investigated by using impedance spectroscopy. Comparison of the effect of annealing temperature on electrical conductivity shows a very interesting behavior. As the annealing temperature increases, the DC conductivity value increases, reaching a maximum at a temperature of 500 °C. However, further increase in the annealing temperature causes a steady decrease in the DC conductivity.

Purpose Patients with known coronary artery disease (CAD) comprise a heterogenous population with varied clinical and imaging characteristics. Unsupervised machine learning can identify new risk phenotypes in an unbiased fashion. We use cluster analysis to risk-stratify patients with known CAD undergoing single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). Methods From 37,298 patients in the REFINE SPECT registry, we identified 9221 patients with known coronary artery disease. Unsupervised machine learning was performed using clinical (23), acquisition (17), and image analysis (24) parameters from 4774 patients (internal cohort) and validated with 4447 patients (external cohort). Risk stratification for all-cause mortality was compared to stress total perfusion deficit ( Results Three clusters were identified, with patients in Cluster 3 having a higher body mass index, more diabetes mellitus and hypertension, and less likely to be male, have dyslipidemia, or undergo exercise stress imaging (p p p p Conclusions Our unsupervised cluster analysis in patients with known CAD undergoing SPECT MPI identified three distinct phenotypic clusters and predicted all-cause mortality better than ischemia alone.

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This study aimed to compare the biomass obtained via the biogasification of straw with the classic bedding material, wheat straw. It was divided into two stages. In the first stage, a laboratory evaluation of the bedding materials was carried out, taking into account dry matter, pH, and water absorption. In the laboratory tests, the bedding obtained after the biogasification of straw (Verbio) showed better sorptive properties, with a value of 439.86% (wheat straw’s value was 294.10%), and its pH value was higher than that of wheat straw. In the second stage of the experiment, field tests were carried out on a production farm, wherein the bedding was evaluated for bedding hygiene, animal hygiene, insulation properties, animal productivity, and microbiological properties. A microbiological assessment was also performed. Regarding cleanliness and production parameters and thermographic insulation properties, the two types of bedding did not show statistically significant differences. In terms of microbiological parameters, a higher number of all examined types of bacteria and fungi was observed in the Verbio bedding compared with straw, but these differences were not statistically significant, except in the case of total coliform. The results indicate that straw obtained after gasification is a suitable bedding material, with parameters similar to those of wheat straw.

This document outlines the important aspects of caring for patients who have been diagnosed with advanced pelvic cancer. It is primarily aimed at those who are establishing a service that adequately caters to this patient group. The relevant literature has been summarized and an attempt made to simplify the approach to management of these complex cases.

Lateral pelvic lymph node (LPLN) metastases are an important cause of preventable local failure in rectal cancer. The aim of this study was to evaluate clinical and oncological outcomes following magnetic resonance imaging (MRI)-directed surgical selection for lateral pelvic lymph node dissection (LPLND) after total neoadjuvant therapy (TNT).A retrospective consecutive cohort analysis was performed of rectal cancer patients with enlarged LPLN on pretreatment MRI. Patients were categorized as LPLND or non-LPLND. The main outcomes were lateral local recurrence rate, perioperative and oncological outcomes and factors associated with decision making for LPLND.A total of 158 patients with enlarged pretreatment LPLN and treated with TNT were identified. Median follow-up was 20 months (interquartile range 10-32). After multidisciplinary review, 88 patients (56.0%) underwent LPLND. Mean age was 53 (SD±12) years, and 54 (34.2%) were female. Total operative time (509 vs 429 minutes; P =0.003) was greater in the LPLND group, but median blood loss ( P =0.70) or rates of major morbidity (19.3% vs 17.0%) did not differ. LPLNs were pathologically positive in 34.1%. The 3-year lateral local recurrence rates (3.4% vs 4.6%; P =0.85) did not differ between groups. Patients with LPLNs demonstrating pretreatment heterogeneity and irregular margin (odds ratio, 3.82; 95% confidence interval: 1.65-8.82) or with short-axis ≥5 mm post-TNT (odds ratio 2.69; 95% confidence interval: 1.19-6.08) were more likely to undergo LPLND.For rectal cancer patients with evidence of LPLN metastasis, the appropriate selection of patients for LPLND can be facilitated by a multidisciplinary MRI-directed approach with no significant difference in perioperative or oncologic outcomes.

PURPOSE: The COVID-19 pandemic has resulted in significant changes in health care delivery, including the rapid adoption of telemedicine across multiple specialties and practice environments. This includes postoperative visits (POV), despite limited data on outcomes following these telemedicine POV. We sought to determine whether these types of visits successfully identify and address postoperative complications when compared with in-person POV. METHODS: This was a retrospective cohort study of patients undergoing elective inpatient cancer-related surgery from March 2020 through December 2020. The exposure variable was type of POV (telemedicine v in-person). The primary outcome was unplanned hospital readmission within 90 days, and secondary outcomes included 30-day readmission, length of stay of first readmission, and mortality. RESULTS: Five-hundred thirty-five patients underwent elective inpatient operations and met our inclusion criteria. Of these, 98 (18.5%) had an initial telemedicine POV. There was no difference in 90-day readmission on the basis of POV type (16.3% telemedicine v 16.5% in-person, P = .99). Reasons for readmission did not differ between patients who underwent a telemedicine POV compared with in-person POV (all P > .05). After adjustment for patients' demographic and clinical factors, telemedicine POV was not associated with 90-day readmission (odds ratio, 0.89; 95% CI, 0.43 to 1.70; P = .77). CONCLUSION: Telemedicine POV use adopted during the COVID-19 pandemic did not increase risk of readmission when compared with in-person visits following inpatient oncologic surgery. These data can help inform policy on the continued use and application of telemedicine after the pandemic.

We designed a prospective feasibility study to assess the 5x-multiplier (5x) calculation (eg, 3 pills in last 24 hours × 5 = 15) to standardize discharge opioid prescriptions compared to usual care.Faculty-based surgical teams volunteered for either 5x or usual care arms. Patients undergoing inpatient (≥ 48 hours) surgery and discharged by surgical teams were included. The primary end point was discharge oral morphine equivalents. Secondary end points were opioid-free discharges and 30-day refill rates.Median last 24-hour oral morphine equivalents was similar between arms (7.5 mg 5x vs 10 mg usual care, P = .830). Median discharge oral morphine equivalents were less in the 5x arm (50 mg 5x vs 75 mg usual care, P .001). Opioid-free discharges included 33.5% 5x vs 18.0% usual care arm patients (P .001). Thirty-day refill rates were similar (15.3% 5x vs 16.5% usual care, P = .742).The 5x-multiplier was associated with reduced opioid prescriptions without increased refills and can be feasibly implemented across a diverse surgical practice.

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PDF file, 146KB, Selected EDDMs of singlet transitions and empty frontier orbitals for 3.

PDF file, 138KB, Representative Annexin-V flow cytometry results.

PDF file, 105KB, 14N{1H} NMR spectra of unlabelled and 15N-NH3 labelled 3.

PDF file, 121KB, 14N {1H} NMR spectra monitoring the irradiation of 3 in buffered solution.

PDF file, 150KB, Effect of complex 3 on nuclear morphology of A2780 & A2780CIS cells.

Photoactivatable PtIV diazido complexes have unusual photobiologic properties. We show here that trans,trans,trans-[PtIV(N3)2(OH)2(py)(NH3)] complex 3 is a potent photoactivated cytotoxin toward human cancer cells in culture, with an average IC50 value in 13 cell lines of 55 ± 28 μmol/L after 30 minutes (0.12 mW/cm2) photoactivation with UVA, although visible light was also effective. Photoactivated complex 3 was noncross-resistant to cisplatin in 3 of 4 resistant cell lines. Cell swelling but very little blebbing was seen for HL60 cells treated with irradiated complex 3. Unlike cisplatin and etoposide, both of which cause apoptosis in HL60 cells, no apoptosis was observed for UVA-activated complex 3 by the Annexin V/propidium iodide flow cytotometry assay. Changes in the levels of the autophagic proteins LC3B-II and p62 in HL60 cells treated with UVA-activated complex 3 indicate autophagy is active during cell death. In a clonogenic assay with the SISO human cervix cancer cell line, 3 inhibited colony formation when activated by UVA irradiation. Antitumor activity of complex 3 in mice bearing xenografted OE19 esophageal carcinoma tumors was photoaugmented by visible light. Insights into the novel reaction pathways of complex 3 have been obtained from 14N{1H} nuclear magnetic resonance studies, which show that photoactivation pathways can involve release of free azide in buffered solution. Density functional theory (DFT) and time-dependent DFT calculations revealed the dissociative character of singlet and triplet excited states of complex 3, which gives rise to reactive, possibly cytotoxic azidyl radicals. Mol Cancer Ther; 11(9); 1894–904. ©2012 AACR.

PDF file, 73KB, Calculated and experimental absorption spectra of 3.

The influence of ionizing radiation on the physicochemical properties of quercetin and rutin in the solid state was studied. Quercetin and rutin were irradiated with the standard recommended radiation dose (25 kGy) according to EN 522 standard. The samples were irradiated by electron beam radiation. EPR studies indicate the formation of a small number of free radicals due to irradiation. Moreover, some radicals recombined with the mean lifetime of 1200 and 93 h, and a stable radical concentration reached only 0.29 and 0.90 ppm for quercetin and rutin, respectively. The performed spectroscopic study (FT-IR) confirmed the radiostability of the flavonoids tested. Chromatographic tests (HPLC, HPLC-MS) showed that irradiation of quercetin and rutin with a 25 kGy dose did not change the physicochemical properties of the tested compounds. Degradation products were not observed. The antioxidant activities were determined by the 2,2-diphenyl-1-pycrylhydrazyl (DPPH) free radical scavenging activity assay, ABTS Radical Scavenging Assay (ABTS), Ferric Reducing Antioxidant Power Assay (FRAP), Cupric Ion Reducing Antioxidant Capacity Assay (CUPRAC). The conducted research confirmed that exposure to ionizing radiation does not change the chemical structure of tested flavonoids and their antioxidant properties.

The Omicron variant of SARS-CoV-2 infected many vaccinated and convalescent individuals1–3. Despite the reduced protection from infection, individuals who received three doses of an mRNA vaccine were highly protected from more serious consequences of infection4. Here we examine the memory B cell repertoire in a longitudinal cohort of individuals receiving three mRNA vaccine doses5,6. We find that the third dose is accompanied by an increase in, and evolution of, receptor-binding domain (RBD)-specific memory B cells. The increase is due to expansion of memory B cell clones that were present after the second dose as well as the emergence of new clones. The antibodies encoded by these cells showed significantly increased potency and breadth when compared with antibodies obtained after the second dose. Notably, the increase in potency was especially evident among newly developing clones of memory cells, which differed from persisting clones in targeting more conserved regions of the RBD. Overall, more than 50% of the analysed neutralizing antibodies in the memory compartment after the third mRNA vaccine dose neutralized the Omicron variant. Thus, individuals receiving three doses of an mRNA vaccine have a diverse memory B cell repertoire that can respond rapidly and produce antibodies capable of clearing even diversified variants such as Omicron. These data help to explain why a third dose of a vaccine that was not specifically designed to protect against variants is effective against variant-induced serious disease.

Aim: At presentation, 15–20% of patients with rectal cancer already have synchronous liver metastases. The aim of this study was to determine the surgical and survival outcomes in patients with advanced rectal cancer who underwent combined pelvic exenteration and liver (oligometastatic) resection. Method: Data from 20 international institutions that performed simultaneous pelvic exenteration and liver resection between 2007 and 2017 were accumulated. Primarily, we examined perioperative outcomes, morbidity and mortality. We also assessed the impact that margin status had on survival. Results: Of 128 patients, 72 (56.2%) were men with a median age of 60 years [interquartile range (IQR) 15 years]. The median size of the liver oligometastatic deposits was 2 cm (IQR 1.8 cm). The median duration of surgery was 406 min (IQR 240 min), with a median blood loss of 1090 ml (IQR 2010 ml). A negative resection margin (R0 resection) was achieved in 73.5% of pelvic exenterations and 66.4% of liver resections. The 30-day mortality rate was 1.6%, and 32% of patients had a major postoperative complication. The 5-year overall survival for patients in whom an R0 resection of both primary and metastatic disease was achieved was 54.6% compared with 20% for those with an R1/R2 resection (P = 0.006). Conclusion: Simultaneous pelvic exenteration and liver resection is feasible, with acceptable morbidity and mortality. Simultaneous resection should only be performed where an R0 resection of both pelvic and hepatic disease is anticipated.

The potassium channel opening drugs flupirtine and retigabine have been withdrawn from the market due to occasional drug-induced liver injury (DILI) and tissue discoloration, respectively. While the mechanism underlying DILI after prolonged flupirtine use is not entirely understood, evidence indicates that both drugs are metabolized in an initial step to reactive

Background Although intensity-modulated radiation therapy (IMRT) is considered the standard of care for the treatment of squamous cell carcinoma of the anus (SCCA), few large series have reported oncologic outcomes and toxicities. In this retrospective report, we aim to describe outcomes and toxicities after IMRT-based chemoradiation (CRT) for the treatment of SCCA, evaluate the impact of dose escalation (>54 Gy), and compare concurrent fluoropyrimidine in combination with either mitomycin or with cisplatin as chemosensitizers. Methods Patients treated at The University of Texas MD Anderson Cancer Center between January 1, 2003 and December 31, 2018 with IMRT-based CRT were included. Median time to locoregional recurrence, time to colostomy, and overall survival were estimated using the Kaplan–Meier method. Results A total of 428 patients were included; median follow-up was 4.4 years. Three hundred and thirty-four patients (78.0%) were treated with concurrent cisplatin and fluoropyrimidine, and 160 (37.4%) with >54 Gy. Two- and 5-year freedom from locoregional failure, freedom from colostomy failure, and overall survival were 86.5% and 81.2%, respectively, 90.0% and 88.3%, respectively, and 93.6% and 85.8%, respectively. Neither dose escalation nor mitomycin-based concurrent chemotherapy resulted in improved outcomes. Mitomycin-based concurrent chemotherapy was associated with in approximately 2.5 times increased grade 3 or greater acute toxicity. Radiation dose >54 Gy was associated with approximately 2.6 times increased Grade 3 or greater chronic toxicity. Conclusions Our results suggest IMRT-based CRT with concurrent fluoropyrimidine and cisplatin is a safe and feasible option for patient with SCCA and may cause less acute toxicity. The role for radiation dose escalation is unclear and requires further study.

The global increase in mobile technology usage has created a need for better energy storage systems. With standard batteries reaching their technological limits, alternate energy storage methods are gaining momentum. In this study, we demonstrate a cheap and efficient way of building from scratch high-performance supercapacitors based on graphene oxide (GO) functionalized with tetrapyrrole derivatives: porphyrins and phthalocyanines. We present supercapacitors with capacitances about 30 times larger than those of the pristine graphene oxide-based counterparts. Experimental characterisation methods including X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), ultraviolet-visible spectroscopy (UV-VIS), electron paramagnetic resonance (EPR), and density functional theory (DFT) calculations revealed correlations between the structural, magnetic, electronic and thermodynamic properties of these materials and their performance as supercapacitors. Electrochemical studies indicate the complex and versatile nature of capacitive effects associated with thin layers of supramolecular composites of graphene oxide. The electrical double layer (EDL) capacitance, cation intercalation and faradaic processes are coupled. Moreover, differences in the electronic interactions between GO and tetrapyrrolic modifiers have a profound effect on the observed capacitance. At the same time, these interactions are sufficiently weak to induce only subtle spectral changes, as well as a small increase of the interlayer distance as determined by XRD measurements. The present work offers a viable strategy for manufacturing high-performance supercapacitive materials that are superior to the state of the art nanocarbon-based supercapacitors using benign electrolytes in terms of capacitance per mass unit and have the potential for application in future green energy storage technologies. Our study provides insight into the multifarious origins of supercapacitance beyond the well-known EDL mechanism.

PurposeDepressive disorder is common among hemodialysis (HD) patients and is associated with higher mortality rate. However, depression screening and treatment in dialysis population remains insufficient. The aim of the study was to show the prevalence of depression in patients on maintenance HD and to discuss the proper diagnostic approach, including dementia screening.Patients and methodsWe conducted a cross-sectional study that included 103 HD patients from one Dialysis Centre in Gdańsk (Poland). Cognitive functions were evaluated using Mini–Mental State Examination (MMSE). The screening for depression was assessed using Beck Depression Inventory (BDI-II). The diagnosis of depressive disorder was confirmed and its severity evaluated by psychiatrists based upon clinical assessment and scales. Sociodemographic, laboratory and dialysis data were also collected.ResultsAccording to BDI-II depressive symptoms were present in 43% of patients while the diagnosis of clinical Major Depressive Disorder (MDD) was confirmed by the psychiatrists in 13% of all subjects. In the depressive disorder group there was a prevalence of female and patients suffering from diabetes mellitus, levels of calcium phosphate index (CaxPi) were higher and Kt/V was lower. The optimal cut- off score for diagnosing major depressive disorder using BDI-II was ≥ 20 points. Cognitive impairment on the level of major neurocognitive disorder (dementia) was found in 18 % of the study group.ConclusionsThe prevalence of depression assessed using self- or clinician-administered questionnaires was higher than reported by clinical interview performed by the psychiatrist. Higher scores of CaxPi and lower Kt/V in depressive patients may suggest worse compliance in this group. The psychiatrist’s examination as a part of care at the Dialysis Centre could improve diagnosis of depression and its treatment with the goal to improve quality of life and lower the mortality rate in this population.

The article presents research on the performance of different distributed fibre optic sensing (DFOS) tools, including both layered cables and monolithic composite sensors. The main need for the presented research was related to the growing applications of the DFOS techniques for the measurements of cracked concrete structures. There are no clear guidelines on the required parameters of the DFOS tools, which, despite their different designs, are offered for the same purpose (strain sensing). The state-of-the-art review and previous experiences show noticeable differences in the quality of the results depending on the applied DFOS tool. The technical construction of selected solutions was described with its theoretical consequences, and then laboratory tests on full-size reinforced concrete beams were discussed. Beams equipped with embedded tools were investigated in four-point bending tests, causing the formation of multiple cracks in the tension zone along the beams’ length. The results in the form of strain profiles registered by selected DFOS tools were analysed regarding the qualitative (crack detection) and quantitative (width estimation) crack assessment. The comparison between crack-induced strain profiles was based on a new parameter called crack shape coefficient CSC, which could be applied to assess the effectiveness of the particular DFOS tool in crack detection and analysis. It was one of the world’s first research allowing for such direct comparison between the layered and monolithic sensing tools. The summary indicates practical guidelines referring to the preferable design of the tools best suitable for crack measurements, as well as the field proofs based on data from two concrete bridges in Germany.

**Background** Population-based serological studies allow to estimate prevalence of SARS-CoV-2 infections despite a substantial number of mild or asymptomatic disease courses. This became even more relevant for decision making after vaccination started. The KoCo19 cohort tracks the pandemic progress in the Munich general population for over two years, setting it apart in Europe. **Methods** Recruitment occurred during the initial pandemic wave, including 5313 participants above 13 years from private households in Munich. Four follow-ups were held at crucial times of the pandemic, with response rates of at least 70%. Participants filled questionnaires on socio-demographics and potential risk factors of infection. From Follow-up 2, information on SARS-CoV-2 vaccination was added. SARS-CoV-2 antibody status was measured using the Roche Elecsys® Anti-SARS-CoV-2 anti-N assay (indicating previous infection) and the Roche Elecsys® Anti-SARS-CoV-2 anti-S assay (indicating previous infection and/or vaccination). This allowed us to distinguish between sources of acquired antibodies. **Results** The SARS-CoV-2 estimated cumulative sero-prevalence increased from 1.6% (1.1-2.1%) in May 2020 to 14.5% (12.7-16.2%) in November 2021. Underreporting with respect to official numbers fluctuated with testing policies and capacities, becoming a factor of more than two during the second half of 2021. Simultaneously, the vaccination campaign against the SARS-CoV-2 virus increased the percentage of the Munich population having antibodies, with 86.8% (85.5-87.9%) having developed anti-S and/or anti-N in November 2021. Incidence rates for infections after (BTI) and without previous vaccination (INS) differed (ratio INS/BTI of 2.1, 0.7-3.6). However, the prevalence of infections was higher in the non-vaccinated population than in the vaccinated one. Considering the whole follow-up time, being born outside Germany, working in a high-risk job and living area per inhabitant were identified as risk factors for infection, while other socio-demographic and health-related variables were not. Although we obtained significant within-household clustering of SARS-CoV-2 cases, no further geospatial clustering was found. **Conclusions** Vaccination increased the coverage of the Munich population presenting SARS-CoV-2 antibodies, but breakthrough infections contribute to community spread. As underreporting stays relevant over time, infections can go undetected, so non-pharmaceutical measures are crucial, particularly for highly contagious strains like Omicron.

Many studies have shown the high efficacy of histamine H3 receptor ligands in preventing weight gain. In addition to evaluating the efficacy of future drug candidates, it is very important to assess their safety profile, which is established through numerous tests and preclinical studies. The purpose of the present study was to evaluate the safety of histamine H3/sigma-2 receptor ligands by assessing their effects on locomotor activity and motor coordination, as well as on the cardiac function, blood pressure, and plasma activity of certain cellular enzymes. The ligands tested at a dose of 10 mg/kg b.w. did not cause changes in locomotor activity (except for KSK-74) and did not affect motor coordination. Significant reductions in blood pressure were observed after the administration of compounds KSK-63, KSK-73, and KSK-74, which seems logically related to the increased effect of histamine. Although the results of in vitro studies suggest that the tested ligands can block the human ether-a-go-go-related gene (hERG) potassium channels, they did not affect cardiac parameters in vivo. It should be noted that repeated administration of the tested compounds prevented an increase in the activity of alanine aminotransferase (AlaT) and gamma-glutamyl transpeptidases (gGT) observed in the control animals fed a palatable diet. The obtained results show that the ligands selected for this research are not only effective in preventing weight gain but also demonstrate safety in relation to the evaluated parameters, allowing the compounds to proceed to the next stages of research.