Novel Strategy in the Detection of Adverse Cutaneous Drug Reactions: A Case Series Study.

With multimorbidity on the rise, adverse cutaneous drug reactions are becoming a daily challenge in clinical practice. The objective evaluation of the skin lesion is crucial but hardly realized due to missing technology and guidelines. In this study, the novel Dermus SkinScanner-U, an optically guided high-frequency ultrasound imaging device, was evaluated regarding its comparability with the Dermatology Life Quality Index (DLQI) and the pharmacological analysis of the patients' drug therapy. A total of 40 adult patients were evaluated, all with chronic medication use and skin lesions that led to non-compliance toward the pharmacotherapy. With the ongoing aim of further improving the methodology, the first results, with two detailed patient cases, are presented here. It was concluded that in the cases evaluated, there was a significant correlation between the characteristics of the lesions observed on the optical and ultrasound image, the DLQI score, and the pharmacological analysis. The next steps include increasing the scale of the study to ultimately develop a quality-assured methodology for the correct diagnosis of skin-related adverse drug reactions and to prepare a database with the most frequently observed events.

Evaluating the dynamics and efficacy of a live, attenuated Mycoplasma anserisalpingitidis vaccine candidate under farm conditions.

The aim of the present study was to monitor the dynamics and to measure the safety and efficacy of a live, attenuated, thermosensitive Mycoplasma anserisalpingitidis vaccine candidate, namely MA271, in geese breeder flocks under field conditions. Two rearing flocks were vaccinated with MA271 at 4 weeks of age and boosted at 24 weeks of age by cloaca inoculation (1 ml) and eye-dropping (60 µl). The geese then were transported to multi-aged breeding farms. Two breeding flocks served as controls. Colonization of the cloaca by MA271 showed 75% maximum prevalence between 4 and 6 weeks after the first vaccination. Then the prevalence decreased to 25% until the cooler, humid fall months which coincided with the booster vaccination. Boosting raised cloacal colonization to 100%. No clinical signs were observed in the vaccinated birds. After transportation to five multi-aged breeding farms, the wild-type strain appeared as well as MA271 in three flocks. In one flock, the wild-type strain completely displaced MA271, while in one flock only MA271 was detected. Only wild-type strains were detected in the control flocks; however, due to an HPAI outbreak, both flocks were exterminated before the end of the study. Based on the available data, the median percentage of infertile eggs was 3.7-5.1% in the MA271 vaccinated flocks, and 7.7% in the non-vaccinated flock. In conclusion, MA271 can colonize the cloaca of geese under field conditions. MA271 proved to be safe and presumably protects against M. anserisalpingitidis-induced reproduction losses.

COVID-19 and Antipsychotic Therapy: Unraveling the Thrombosis Risk.

In the context of the COVID-19 pandemic, this study investigates the potential correlation between the increased use of antipsychotic medications and the rising incidence of venous thromboembolism (VTE). As psychiatric disorders surged, the consequential escalation in antipsychotic drug use raised concerns about thrombotic risks. We conducted a comprehensive literature review using PubMed, focusing on articles that intersected COVID-19, antipsychotic medication, and thrombosis. This approach allowed for a nuanced examination of the historical and recent data on antipsychotic drugs and their association with thrombotic events. Our findings reveal a notable link between the use of antipsychotic medications, particularly second-generation antipsychotics, and an increased risk of VTE, including pulmonary embolism and deep vein thrombosis. This association was evident, despite variations in study designs and populations. The study underscores the need for cautious medication management in psychiatric care, especially during pandemic conditions like COVID-19, to mitigate thrombotic risks. It advocates a personalized approach to prescribing antipsychotics, considering individual patient factors and comorbidities, to balance the benefits against potential thrombotic complications.

Antiviral Potential of Azelastine against Major Respiratory Viruses.

The Coronavirus Disease 2019 (COVID-19) pandemic and the subsequent increase in respiratory viral infections highlight the need for broad-spectrum antivirals to enable a quick and efficient reaction to current and emerging viral outbreaks. We previously demonstrated that the antihistamine azelastine hydrochloride (azelastine-HCl) exhibited in vitro antiviral activity against SARS-CoV-2. Furthermore, in a phase 2 clinical study, a commercial azelastine-containing nasal spray significantly reduced the viral load in SARS-CoV-2-infected individuals. Here, we evaluate the efficacy of azelastine-HCl against additional human coronaviruses, including the SARS-CoV-2 omicron variant and a seasonal human coronavirus, 229E, through in vitro infection assays, with azelastine showing a comparable potency against both. Furthermore, we determined that azelastine-HCl also inhibits the replication of Respiratory syncytial virus A (RSV A) in both prophylactic and therapeutic settings. In a human 3D nasal tissue model (MucilAirTM-Pool, Epithelix), azelastine-HCl protected tissue integrity and function from the effects of infection with influenza A H1N1 and resulted in a reduced viral load soon after infection. Our results suggest that azelastine-HCl has a broad antiviral effect and can be considered a safe option against the most common respiratory viruses to prevent or treat such infections locally in the form of a nasal spray that is commonly available globally.

Anti-Toxin Responses to Natural Enterotoxigenic Escherichia coli (ETEC) Infection in Adults and Children in Bangladesh.

A sero-epidemiology study was conducted in Dhaka, Bangladesh between January 2020 and February 2021 to assess the immune responses to ETEC infection in adults and children. (1) Background: Enterotoxigenic Escherichia coli infection is a main cause of diarrheal disease in endemic countries. The characterization of the immune responses evoked by natural infection can guide vaccine development efforts. (2) Methods: A total of 617 adult and 480 pediatric diarrheal patients were screened, and 43 adults and 46 children (below 5 years of age) with an acute ETEC infection completed the study. The plasma samples were analyzed for antibody responses against the ETEC toxins. (3) Results: Heat-stable toxin (ST)-positive ETEC is the main cause of ETEC infection in adults, unlike in children in an endemic setting. We detected very low levels of anti-ST antibodies, and no ST-neutralizing activity. However, infection with ETEC strains expressing the heat-labile toxin (LT) induced systemic antibody responses in less than 25% of subjects. The antibody levels against LTA and LTB, as well as cholera toxin (CT), correlated well. The anti-LT antibodies were shown to have LT- and CT- neutralizing activity. The antibody reactivity against linear LT epitopes did not correlate with toxin-neutralizing activity. (4) Conclusions: Unlike LT, ST is a poor antigen and even adults have low anti-ST antibody levels that do not allow for the detection of toxin-neutralizing activity.

The Possible Clinical Significance of a Decreased Serum Level of Soluble PD-L1 in Discoid Lupus Erythematosus, but Not in Subacute Cutaneous Lupus Erythematosus-A Pilot Study.

Cutaneous lupus erythematosus (CLE) is an autoimmune skin disease with various clinical forms, including the subtypes of discoid lupus erythematosus (DLE) and subacute cutaneous lupus erythematosus (SCLE). The altered function of the programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) axis in CLE pathogenesis has been suggested. Here, the soluble forms of PD-1 (sPD-1) and PD-L1 (sPD-L1) were explored in untreated DLE and SCLE. Levels of sPD-1 and sPD-L1 were determined by enzyme-linked immunosorbent assay in serums of 21 DLE, 18 SCLE, 13 systemic lupus erythematosus (SLE) patients and 20 healthy controls (HCs). Differences between patient groups and HCs, and the association between clinical activity of skin symptoms and sPD-1/sPD-L1 levels were analyzed with Mann-Whitney U-test and Spearmann's correlation. Regarding sPD-1 levels, no statistically significant differences were found between DLE and SCLE groups, nor compared to HCs. As for sPD-L1, a significantly lower level was found in the DLE group compared to the SCLE and HC groups (p = 0.027 and p = 0.009, respectively). In SLE, significantly higher sPD-1 was found compared to HCs (p = 0.002). No association between skin symptom activity and sPD-1/sPD-L1 levels was found in CLE. Alterations of the inhibitory effect of sPD-L1 on T-cell activity might elucidate the differences between DLE and SCLE.

Phenotypic and genetic insights into efflux pump mechanism in Mycoplasma anserisalpingitidis.

Introduction: Mycoplasma anserisalpingitidis is one of the most important waterfowl-pathogenic mycoplasmas. Due to inadequate antibiotic treatment, many strains with high minimal inhibitory concentration (MIC) values for multiple drugs have been isolated lately. Decreased antibiotic susceptibility in several Mycoplasma species are known to be associated with mutations in topoisomerase and ribosomal genes, but other strategies such as active efflux pump mechanisms were also described. The scope of this study was the phenotypic and genetic characterization of the active efflux mechanism in M. anserisalpingitidis. Methods: We measured the MIC values in the presence and absence of different efflux pump inhibitors (EPIs), such as carbonyl cyanide m-chlorophenylhydrazine (CCCP), orthovanadate (OV), and reserpine (RSP). Moreover, bioinformatic tools were utilized to detect putative regulatory sequences of membrane transport proteins coding genes, while comparative genome analysis was performed to reveal potential markers of antibiotic resistance. Results: Out of the three examined EPIs, CCCP decreased the MICs at least two-fold below the original MICs (in 23 cases out of 36 strains). In the presence of OV or RSP, MIC value differences could be seen only if modified dilution series (10% decrease steps were used instead of two-fold dilutions) were applied (in 24/36 cases with OV and 9/36 with RSP). During comparative genome analysis, non-synonymous single nucleotide polymorphisms (nsSNPs) were identified in genes encoding ABC membrane transport proteins, which were displayed in higher percentages in M. anserisalpingitidis strains with increased MICs. In terms of other genes, a nsSNP was identified in DNA gyrase subunit A (gyrA) gene which can be related to decreased susceptibility to enrofloxacin. The present study is the first to highlight the importance of efflux pump mechanisms in M. anserisalpingitidis. Discussion: Considering the observed effects of the EPI CCCP against this bacterium, it can be assumed, that the use of EPIs would increase the efficiency of targeted antibiotic therapy in the future control of this pathogen. However, further research is required to obtain a more comprehensive understanding of efflux pump mechanism in this bacterium.

A comparative study of femtosecond pulsed laser ablation of meloxicam in distilled water and in air.

The increasing prevalence of water insoluble or poorly soluble drugs calls for the development of new formulation methods. Common approaches include the reduction of particle size and degree of crystallinity. Pulsed laser ablation is a clean technique for producing sub-micrometre sized drug particles and has the potential to induce amorphization. We studied the effect of femtosecond pulsed laser ablation (ELI ALPS THz pump laser system: λc = 781 nm, τ = 135 fs) on meloxicam in distilled water and in air. The ablated particles were characterized chemically, morphologically and in terms of crystallinity. We demonstrated that femtosecond laser ablation can induce partial amorphization of the particles in addition to a reduction in particle size. In the case of femtosecond pulsed laser ablation in air, the formation of pure meloxicam spheres showed that this technique can produce amorphous meloxicam without the use of excipients, which is a unique result. We also aimed to describe the ablation processes in both investigated media.

Hatchability of Fascioloides magna Eggs in Cervids.

The giant liver fluke (Fascioloides magna) is an invasive parasite found permanently in three foci in Europe. The fluke has an indirect life cycle involving a final and an intermediate host. The currently accepted terminology determines three types of final hosts: definitive, dead-end, and aberrant hosts. Recently, roe deer (Capreolus capreolus) has been classified as an aberrant host, which cannot contribute to the reproduction of F. magna. This study investigated the hatchability of F. magna eggs of red deer (Cervus elaphus) and roe deer origin to compare the suitability of the two host species for the maintenance of the parasite. The study was carried out on a newly invaded area, two years after the first reported observation of F. magna. The prevalence of the parasite proved to be 68.4% (CI95% 44.6-85.3%) in red deer and 36.7% (CI95% 24.8-50.0%) in roe deer. The difference between the two species was confirmed to be significant (p = 0.02). The mean intensity proved to be 10.0 (CI95% 4.9-22.6) and 7.59 (CI95% 2.7-24.2) in the red deer and the roe deer, respectively. The difference of the mean intensities did not prove to be significant (p = 0.72). Of the 70 observed pseudocysts, 67 originated from red deer and 3 from roe deer. Most of the pseudocysts contained two flukes, while a few pseudocysts contained one or three parasites. Egg production was observed in all three types of pseudocysts. We did not find more than three flukes in any pseudocyst. The apparent proportion of self-fertilisation in flukes without mating partners was 23.5% and 100% in red deer and roe deer, respectively. The survival of single-parent eggs was not confirmed to be worse than that of gregarious parents. The viability of offspring originating from roe and red deer differed significantly. Our findings suggest that F. magna adapted to the new populations of susceptible hosts rather than vice versa.

The "cardiac neglect": a gentle reminder to radiologists interpreting contrast-enhanced abdominal MDCT.

Myocardial infarction (MI) may be visible on contrast-enhanced multidetector computed tomography (MDCT) scans of the abdomen. In the previous literature, potentially missed MI in abdominal MDCTs was not perceived as an issue in radiology. This retrospective single-center study assessed the frequency of detectable myocardial hypoperfusion in contrast-enhanced abdominal MDCTs. We identified 107 patients between 2006 and 2022 who had abdominal MDCTs on the same day or the day before a catheter-proven or clinically evident diagnosis of MI. After reviewing the digital patient records and applying the exclusion criteria, we included 38 patients, with 19 showing areas of myocardial hypoperfusion. All MDCT studies were non ECG-gated. The delay between the MDCT examination and MI diagnosis was shorter in studies with myocardial hypoperfusion (7.4±6.5 hours and 13.8±12.5 hours) but not statistically significant p=0.054. Only 2 of 19 (11%) of these pathologies had been noted in the written radiology reports. The most common cardinal symptom was epigastric pain (50%), followed by polytrauma (21%). STEMI was significantly more common in cases of myocardial hypoperfusion p=0.009. Overall, 16 of 38 (42%) patients died because of acute MI. Based on extrapolations using local MDCT rates, we estimate several thousand radiologically missed MI cases worldwide per year.

The effects of a complex yoga-based intervention on healthy psychological functioning.

Background: Yoga based interventions were found to have a positive impact on various indicators of psychological functioning, such as perceived stress, satisfaction with life, positive and negative affectivity. Additionally, such interventions improved bodily or interoceptive awareness and spirituality. Methods: The present study assessed the effects of a 3-month long complex yoga-based intervention compared to a passive control group in a Hungarian community sample. The final sample consisted of 44 intervention (Mage = 47.5, SD = = 8.76) and 29 control participants (Mage = 47.4, SD = 9.47). The aforementioned constructs were measured 1 week before and after the intervention. Results: The intervention reduced participants' perceived stress (p = <0.001, ηp 2 = 0.153) and negative affectivity (p = 0.019, ηp 2 = 0.113), improved spirituality (p = 0.048, ηp 2 = 0.054) and various aspects of interoceptive awareness such as noticing (p = <0.001, ηp 2 = 0.169) attention regulation (p = <0.001, ηp 2 = 0.211), self-regulation (p = 0.002, ηp 2 = 0.190) body listening (p = 0.010, ηp 2 = 0.097), trusting (p = 0.026, ηp 2 = 0.070), but did not impact positive affectivity and satisfaction with life. Conclusion: A 3-months long complex yoga-based intervention has a positive impact on many aspects of healthy psychological functioning.

Early intervention with azelastine nasal spray may reduce viral load in SARS-CoV-2 infected patients.

With the changing epidemiology of COVID-19 and its impact on our daily lives, there is still an unmet need of COVID-19 therapies treating early infections to prevent progression. The current study was a randomized, parallel, double-blind, placebo-controlled trial. Ninety SARS-CoV-2 positive patients were randomized into 3 groups receiving placebo, 0.02% or 0.1% azelastine nasal spray for 11 days, during which viral loads were assessed by quantitative PCR. Investigators assessed patients' status throughout the trial including safety follow-ups (days 16 and 60). Symptoms were documented in patient diaries. Initial viral loads were log10 6.85 ± 1.31 (mean ± SD) copies/mL (ORF 1a/b gene). After treatment, virus load was reduced in all groups (p < 0.0001) but was greater in the 0.1% group compared to placebo (p = 0.007). In a subset of patients (initial Ct < 25) viral load was strongly reduced on day 4 in the 0.1% group compared to placebo (p = 0.005). Negative PCR results appeared earlier and more frequently in the azelastine treated groups: being 18.52% and 21.43% in the 0.1% and 0.02% groups, respectively, compared to 0% for placebo on day 8. Comparable numbers of adverse events occurred in all treatment groups with no safety concerns. The shown effects of azelastine nasal spray may thus be suggestive of azelastine's potential as an antiviral treatment.Trial registration: The study was registered in the German Clinical Trial Register (DRKS-ID: DRKS00024520; Date of Registration in DRKS: 12/02/2021). EudraCT number: 2020-005544-34.

Sonographic Rectal Enema ("hydrocolon") for Diagnosing Large Bowel Pathologies in Infancy - Pictorial Review to Demonstrate Feasibility and Value.

Bowel pathologies encompass a large diversity of diseases with commonly confusing and overlapping clinical presentations. Sonography has a leading role in diagnosing these disorders, especially in small children. However, in some cases, baseline sonography does not deliver a satisfactory result on the suspected pathology. To increase the sensitivity and specificity of the standard bowel ultrasound technique, complimentary ultrasound enema may be performed, which is also referred to as "hydrocolon" in the literature. This paper summarizes the technique of sonographic enema, as well as some bowel pathologies from our case series where sonographic enema proved to be helpful in the diagnostic work-up.

Paediatric CT made easy.

Paediatric computed tomography (CT) imaging has always been associated with challenges. Although the technical background of CT imaging is complex, it is worth considering the baseline aspects of radiation exposure to prevent unwanted excess radiation in paediatric patients. In this review, we discuss the most relevant factors influencing radiation exposure, and provide a simplified and practical approach to optimise paediatric CT.

Survey of wild boar hunter interactions with pig farming in central Europe.

African swine fever (ASF) is a fatal animal disease without zoonotic potential but greatly impacts human well-being, especially in the most vulnerable human communities. In Europe, ASF concerns mostly the wildlife domain of health. The main vector of the disease is confirmed to be the wild boar, though long-distance jumps of the infection are due to anthropogenic effects. This study aimed to evaluate the potential role of hunting assistant personnel (beaters and carcass handlers) in ASF spread in Hungary. Based on a personal interview survey, we attempted to identify the epidemiological risk caused by hunting activities and the hunting personnel. The interviews with 58 hunting workers confirmed that an extent backyard pig sector (13 pig farmers) and pork production system (31 pork producers) existed within the study region out of the authorities' sight. Two pig farmers did not wear special working clothes for pig caring, seven pork producers disposed of slaughter offal in the settlements periphery, and six persons regularly contacted distant pig farms. The revealed knowledge, attitude, and practice of the questioned pig farmers suggested that this sector would be very vulnerable in an epidemic situation; moreover, backyard farms would cause a great risk for wildboar populations. Considering that the study region is the third poorest region of Hungary, these findings called attention to the high epidemiologic risk of socioeconomic inequality between different regions within the European Union.

Pharmacometric Modeling of the Impact of Azelastine Nasal Spray on SARS-CoV-2 Viral Load and Related Symptoms in COVID-19 Patients.

The histamine-1 receptor antagonist azelastine was recently found to impact SARS-CoV-2 viral kinetics in a Phase 2 clinical trial (CARVIN). Thus, we investigated the relationship between intranasal azelastine administrations and viral load, as well as symptom severity in COVID-19 patients and analyzed the impact of covariates using non-linear mixed-effects modeling. For this, we developed a pharmacokinetic (PK) model for the oral and intranasal administration of azelastine. A one-compartment model with parallel absorption after intranasal administration described the PK best, covering both the intranasal and the gastro-intestinal absorption pathways. For virus kinetic and symptoms modeling, viral load and symptom records were gathered from the CARVIN study that included data of 82 COVID-19 patients receiving placebo or intranasal azelastine. The effect of azelastine on viral load was described by a dose-effect model targeting the virus elimination rate. An extension of the model revealed a relationship between COVID-19 symptoms severity and the number of infected cells. The analysis revealed that the intranasal administration of azelastine led to a faster decline in viral load and symptoms severity compared to placebo. Moreover, older patients showed a slower decline in viral load compared to younger patients and male patients experienced higher peak viral loads than females.

Learning rate of students detecting and annotating pediatric wrist fractures in supervised artificial intelligence dataset preparations.

The use of artificial intelligence (AI) in image analysis is an intensively debated topic in the radiology community these days. AI computer vision algorithms typically rely on large-scale image databases, annotated by specialists. Developing and maintaining them is time-consuming, thus, the involvement of non-experts into the workflow of annotation should be considered. We assessed the learning rate of inexperienced evaluators regarding correct labeling of pediatric wrist fractures on digital radiographs. Students with and without a medical background labeled wrist fractures with bounding boxes in 7,000 radiographs over ten days. Pediatric radiologists regularly discussed their mistakes. We found F1 scores-as a measure for detection rate-to increase substantially under specialist feedback (mean 0.61±0.19 at day 1 to 0.97±0.02 at day 10, p<0.001), but not the Intersection over Union as a parameter for labeling precision (mean 0.27±0.29 at day 1 to 0.53±0.25 at day 10, p<0.001). The times needed to correct the students decreased significantly (mean 22.7±6.3 seconds per image at day 1 to 8.9±1.2 seconds at day 10, p<0.001) and were substantially lower as annotated by the radiologists alone. In conclusion our data showed, that the involvement of undergraduated students into annotation of pediatric wrist radiographs enables a substantial time saving for specialists, therefore, it should be considered.

Effect of ractopamine on the release of dopamine from the striatum dissected from mice.

In the past two decades, ractopamine has been used as a feed additive to increase protein synthesis in farmed animals (swine, cattle, and turkeys) and to produce high-quality meat. However, the excessive feeding of animals with ractopamine may result in its accumulation in animal and human tissues after consuming the meat. Ractopamine is a trace amine-associated receptor1 and ß-adrenoceptor agonist banned in the EU but approved in the USA, and it may pose a potential risk to human health. In this paper, the authors, for the first time, provide neurochemical evidence that ractopamine leads to the release of dopamine from nerve terminals of the nigrostriatal pathway in the striatum.