[The history of the institute of higher and additional professional education of the Endocrinology Reserch Centre].

The Endocrinology Reserch Centre is proud not only of its achievements in the area of personalized approach to the examination and treatment of patients in accordance with the principles of evidence-based medicine, the use of modern diagnostic and treatment technologies, but also of its rich history of training scientific and medical personnel. For many years the Center has been attracting the best and most talented graduates of higher medical institutions, becoming the "alma mater" for young doctors - endocrinologists, pediatric endocrinologists and nutritionists. Specialists, graduates of NMRC, make a significant contribution to the development of medicine, conducting research, creating innovative methods of treatment and helping patients not only in our country, but also abroad. However, the State Research Center of the Russian Federation FGBU «NMRC Endocrinology¼ is famous not only for its high-quality and comprehensive training, but also for its experienced, dedicated teaching staff, giving students unique opportunities for professional growth. The purpose of this article is to reflect the most important milestones in the development of education at NMIC Endocrinology, which began its formation more than a century ago, during the most difficult period of transition for our country.

[Meta-analysis of randomized controlled trials of the effectiveness of Prospekta in the treatment of vascular cognitive impairment of varying severity]. / Metaanaliz randomizirovannykh kontroliruemykh issledovanii effektivnosti preparata Prospekta v terapii sosudistykh kognitivnykh narushenii raznoi stepeni vyrazhennosti.

OBJECTIVE: To conduct a meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of Prospekta in the treatment of SCI of varying severity. MATERIAL AND METHODS: The meta-analysis included the results of RCTs of the efficacy of Prospekta in the treatment of VCI, the severity of which was assessed using the Montreal Cognitive Scale (MoCA). The pooled effect estimate included all publications of double-blind, placebo-controlled RCTs that provided sufficient MoCA efficacy data to support further statistical analysis. The main result of the meta-analysis was obtained for the final values of the efficacy indicator in the groups of patients receiving the drug Prospekta, in comparison with the placebo group. RESULTS: A meta-analysis of the effectiveness of Prospekta in the treatment of SCI of varying severity was carried out based on data from 3 RCTs and 2 CTs involving 12.701 patients aged 18 years and older. When using the mixed models method, the effect size for the endpoint «change in total MoCA score from baseline to follow-up visit¼ was 3.4 points for Prospekta (2.7 points for placebo, p<0.0001); for the end point «∆ between changes in the total score on the MoCA scale while taking Prospekta and placebo¼ - 0.6736 points (p<0.0001). CONCLUSION: A statistically significant improvement in cognitive function according to the MoCA scale was demonstrated in patients with VCI using the drug Prospekta.

[Stiff-person syndrome]. / Sindrom rigidnogo cheloveka.

Stiff-person syndrome is a rare autoimmune disorder manifested by stiffness in the trunk and proximal limb muscles and painful muscle spasms in them. The disease is associated with the production of glutamate decarboxylase autoantibodies, an enzyme converting glutamate into gamma-aminobutyric acid. An increase of anti-GAD antibody serum levels above 10.000 IU/mL is specific for stiff-person syndrome. Our own clinical observation of a patient diagnosed with stiff-person syndrome is presented.

Rebound Tremor Frequency as a Potential Diagnostic Marker for Delayed Therapy Escape after Thalamic Deep Brain Stimulation for Essential Tremor-Insights from a Cross-Sectional Study.

Delayed therapy escape (DTE) is frequent after thalamic deep brain stimulation for essential tremor, leading to reduced quality of life, often with ataxic symptoms, and early recognition is challenging. Our goal was to examine whether a low-frequency rebound tremor of the left hand after switching off stimulation is useful as a diagnostic marker for DTE. In this cross-sectional study with additional retrospective analysis, we examined 31 patients with bilateral thalamic DBS ≥ 12 months for essential tremor, using quantitative assessments including video-based motion capture, Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS), and scale for the assessment and rating of ataxia (SARA). If available, preoperative (preOP) and 12-month postoperative assessments were included in the analysis. Evaluations occurred with DBS activated (ON) and deactivated (OFF). A higher ratio FTMTRS nowON/preOP indicated DTE. Preoperative FTMTRS scores were available for 16 patients, including 5 patients with DTE. The receiver operating characteristic analysis found an area under the curve of 0.86 (p = 0.024) for identification of DTE by low-frequency rebound tremor (i.e., OFF) on the left. In conclusion, it could serve as a potential diagnostic marker.

In Search for a Pathogenesis of Major Depression and Suicide-A Joint Investigation of Dopamine and Fiber Tract Anatomy Focusing on the Human Ventral Mesencephalic Tegmentum: Description of a Workflow.

Major depressive disorder (MDD) is prevalent with a high subjective and socio-economic burden. Despite the effectiveness of classical treatment methods, 20-30% of patients stay treatment-resistant. Deep Brain Stimulation of the superolateral branch of the medial forebrain bundle is emerging as a clinical treatment. The stimulation region (ventral tegmental area, VTA), supported by experimental data, points to the role of dopaminergic (DA) transmission in disease pathology. This work sets out to develop a workflow that will allow the performance of analyses on midbrain DA-ergic neurons and projections in subjects who have committed suicide. Human midbrains were retrieved during autopsy, formalin-fixed, and scanned in a Bruker MRI scanner (7T). Sections were sliced, stained for tyrosine hydroxylase (TH), digitized, and integrated into the Montreal Neurological Institute (MNI) brain space together with a high-resolution fiber tract atlas. Subnuclei of the VTA region were identified. TH-positive neurons and fibers were semi-quantitatively evaluated. The study established a rigorous protocol allowing for parallel histological assessments and fiber tractographic analysis in a common space. Semi-quantitative readings are feasible and allow the detection of cell loss in VTA subnuclei. This work describes the intricate workflow and first results of an investigation of DA anatomy in VTA subnuclei in a growing naturalistic database.

Real-world acute toxicity and 90-day mortality in patients with stage I non-small cell lung cancer treated with stereotactic body radiotherapy.

INTRODUCTION: Stereotactic body radiotherapy (SBRT) has firmly established its role in stage I non-small cell lung cancer (NSCLC). Clinical trial results may not fully apply to real-world scenarios. This study aimed to uncover the real-world incidence of acute toxicity and 90-day mortality in SBRT-treated stage I NSCLC patients and develop prediction models for these outcomes. METHODS: Prospective data from the Dutch Lung Cancer Audit for Radiotherapy (DLCA-R) were collected nationally. Patients with stage I NSCLC (cT1-2aN0M0) treated with SBRT in 2017-2021 were included. Acute toxicity was assessed, defined as grade ≥2 radiation-pneumonitis or grade ≥3 non-hematologic toxicity ≤90 days after SBRT. Prediction models for acute toxicity and 90-day mortality were developed and internally validated. RESULTS: Among 7,279 patients, the mean age was 72.5 years, with 21.6% being >80 years. Most were female (50.7%), had WHO scores 0-1 (73.3%), and cT1a-b tumors (64.6%), predominantly in upper lobes (65.2%). Acute toxicity was observed in 280 (3.8%) of patients and 90-day mortality in 122 (1.7%). Predictors for acute toxicity included WHO ≥2, lower FEV1 and DLCO, no pathology confirmation, middle/lower lobe tumor location, cT1c-cT2a stage, and higher mean lung dose (c-statistic 0.68). Female gender, WHO ≥2, and acute toxicity predicted higher 90-day mortality (c-statistic 0.73). CONCLUSIONS: This nationwide study revealed a low rate of acute toxicity and an acceptable 90-day mortality rate in SBRT-treated stage I NSCLC patients. Notably, advanced age did not increase acute toxicity or mortality risk. Our predictive models, with satisfactory performance, offer valuable tools for identifying high-risk patients.

[Alveolar adenoma of the lung]. / Al'veolyarnaya adenoma legkogo.

Alveolar adenoma of the lung is a rare benign tumor first described in 1986. This article presents an observation of alveolar adenoma in a 72-year-old woman. Morphological and immunohistochemical methods of tumor diagnostics, issues of differential diagnosis are analyzed. The necessity of complex examination, including radiation methods, morphologic examination and immunohistochemical diagnostics to exclude other more dangerous diseases is shown.

[ALK-positive anaplastic large cell lymphoma of paranasal sinuses: two cases report and literature review]. / ALK-pozitivnaya anaplasticheskaya krupnokletochnaya limfoma s porazheniem pridatochnykh pazukh nosa: dva klinicheskikh nablyudeniya i obzor literatury.

ALK-positive anaplastic large cell lymphoma is a rare T-cell lymphoma with ALK gene rearrangement that develops in children and young adults. The disease almost always affects the lymph nodes, and extranodal areas are also frequently involved. This article describes two cases of atypical localization of ALK-positive anaplastic large cell lymphoma with involvement of the paranasal sinuses.

Comparative Efficacy of Inhaled and Intravenous Corticosteroids in Managing COVID-19-Related Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition in which the lungs fail to provide sufficient oxygen to the body's vital organs. It is commonly associated with COVID-19 patients. Severe cases of COVID-19 can lead to lung damage and organ failure due to an immune response in the body. To mitigate these effects, corticosteroids, which are known for their anti-inflammatory properties, have been suggested as a potential treatment option. The primary focus of this study was to assess the impact of various corticosteroid administration methods on the outcomes of patients with COVID-19. Methods: The current study was conducted on COVID-19 patients divided into three groups. The first group was administered 6 mg of intravenous (IV) dexamethasone; the second group received 1 mg/kg of IV methylprednisolone (methylprednisolone); and the third group received budesonide respirable solution at a dosage of 1mg twice daily. The neubilizer used was a vibrating mesh nebulizer (VMN). All patients received standard care. We found that dexamethasone administered intravenously led to a significant reduction in C-reactive protein levels, surpassing the effectiveness of both IV methylprednisolone and inhaled budesonide. Oxygen saturation without mask change over time showed statistically significant differences (p = 0.004) in favor of the budesonide and dexamethasone groups for all days. Individuals who received methylprednisolone showed a significant decrease in mortality rate and an extended survival duration, with statistical significance observed at p = 0.024. The rest of the parameters, including ferritin, lymphocytes, total leukocyte count, platelets, hemoglobin, urea, serum potassium, serum sodium, serum creatinine, serum glutamic-pyruvic transaminase, serum glutamic-oxaloacetic transaminase, uric acid, albumin, globulin, erythrocyte sedimentation rate, international normalized ratio, oxygen saturation with flow, and oxygen flow, showed no statistically significant differences between the three drugs. In conclusion, treatment with IV methylprednisolone (1 mg/kg) resulted in a shorter hospital stay, decreased reliance on ventilation, and improved health outcomes for COVID-19 patients compared to using dexamethasone at a daily dosage of 6 mg or budesonide respirable solution at a dosage of 1mg twice daily.

Parkia javanica Edible Pods Reveal Potential as an Anti-Diabetic Agent: UHPLC-QTOF-MS/MS-Based Chemical Profiling, In Silico, In Vitro, In Vivo, and Oxidative Stress Studies.

According to the World Health Organization, over 422 million people worldwide have diabetes, with the majority residing in low- and middle-income countries. Diabetes causes 1.5 million fatalities a year. The number of diabetes cases and its prevalence have progressively increased over the last few decades. This study aims to determine the phytochemicals in the edible part of Perkia javanica, predict their α-glucosidase inhibitory potential, one of the promising targets for diabetes, and then carry out in vitro and in vivo studies. The phytochemicals present in the n-butanol fraction of the methanol extract of P. javanica pods were analyzed using UHPLC-QTOF-MS/MS (Ultra-High-Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry). The UHPLC-QTOF analysis revealed the presence of 79 different compounds in the n-butanol fraction. Among these, six compounds demonstrated excellent binding affinities with α-glucosidase, surpassing the performance of two standard inhibitors, Miglitol and Voglibose. In vitro α-glucosidase inhibitory activities were assessed by the n-butanol fraction, followed by in vivo studies. According to the in vitro study, the inhibitory efficiency against α-glucosidase was determined to have an IC50 value of 261.9 µg/mL. The in vivo findings revealed a significant reduction in blood glucose levels in Swiss albino mice treated with the same extract, decreasing from 462.66 mg/dL to 228.66 mg/dL. Additionally, the extract significantly increased the activity of the enzymes catalase and superoxide dismutase (SOD) and decreased the amount of malondialdehyde (MDA) in the liver and kidney tissue. The predicted physicochemical parameters indicated that most of the compounds would be excreted from the body after inhibition in the small intestine without being absorbed. Considering the low cost and wide availability of raw materials, P. javanica pods can serve as a good food supplement that may help prevent type 2 diabetes management.

Manipulation of feeding patterns in high fat diet fed rats improves microbiota composition dynamics, inflammation and gut-brain signaling.

Chronic consumption of high fat (HF) diets has been shown to increase meal size and meal frequency in rodents, resulting in overeating. Reducing meal frequency and establishing periods of fasting, independently of caloric intake, may improve obesity-associated metabolic disorders. Additionally, diet-driven changes in microbiota composition have been shown to play a critical role in the development and maintenance of metabolic disorders. In this study, we used a pair-feeding paradigm to reduce meal frequency and snacking episodes while maintaining overall intake and body weight in HF fed rats. We hypothesized that manipulation of feeding patterns would improve microbiota composition and metabolic outcomes. Male Wistar rats were placed in three groups consuming either a HF, low fat diet (LF, matched for sugar), or pair-fed HF diet for 7 weeks (n=11-12/group). Pair-fed animals received the same amount of food consumed by the HF fed group once daily before dark onset (HF-PF). Rats underwent oral glucose tolerance and gut peptide cholecystokinin sensitivity tests. Bacterial DNA was extracted from the feces collected during both dark and light cycles and sequenced via Illumina MiSeq sequencing of the 16S V4 region. Our pair-feeding paradigm reduced meal numbers, especially small meals in the inactive phase, without changing total caloric intake. This shift in feeding patterns reduced relative abundances of obesity-associated bacteria and maintained circadian fluctuations in microbial abundances. These changes were associated with improved gastrointestinal (GI) function, reduced inflammation, and improved glucose tolerance and gut to brain signaling. We concluded from these data that targeting snacking may help improve metabolic outcomes, independently of energy content of the diet and hyperphagia.

High-Resolution Geospatial Mapping of Zero-Dose and Underimmunized Children Following Nigeria's 2021 Multiple Indicator Cluster Survey/National Immunization Coverage Survey.

BACKGROUND: "Zero-dose" children are those who are without any routine vaccination or are lacking the first dose of the diphtheria, tetanus, and pertussis-containing vaccine. Based on global estimates from the World Health Organization/United Nations Children's Fund in 2022, Nigeria has the highest number of zero-dose children, with >2.3 million unvaccinated. METHODS: We used data from the 2021 Nigeria Multiple Indicator Cluster Survey/National Immunization Coverage Survey to identify zero-dose and underimmunized children. Geospatial modeling techniques were employed to determine the prevalence of zero-dose children and predict risk areas with underimmunized children at a high resolution (1 × 1 km). RESULTS: Zero-dose and underimmunized children are more prevalent in socially deprived groups. Univariate and multivariate bayesian analyses showed positive correlations between the prevalence of zero-dose and underimmunized children and factors such as stunting, contraceptive prevalence, and literacy. The prevalence of zero-dose and underimmunized children varies significantly by region and ethnicity, with higher rates observed in the country's northern parts. Significant heterogeneity in the distribution of undervaccinated children was observed. CONCLUSIONS: Nigeria needs to enhance its immunization system and coverage. Geospatial modeling can help deliver vaccines effectively to underserved communities. By adopting this approach, countries can ensure equitable vaccine access and contribute to global vaccination objectives.

Results of a 12-Week Open-Label, Non-Interventional Study of the Efficacy and Safety of Olokizumab Therapy in Patients with Rheumatoid Arthritis after Switching from Anti-B-Cell Therapy during the SARS-CoV-2 Pandemic.

ABSTTACT: -The COVID-19 pandemic has significantly changed the understanding of the safety profile of therapies for immunoinflammatory rheumatic diseases (IRDs). This is primarily due to the negative impact of a number of basic disease-modifying antirheumatic drugs (DMARDs) and genetically engineered biological drugs (biological DMARDs, or biologics) on the course and outcomes of a new coronavirus infection. A number of studies have shown that anti-B-cell therapy (rituximab) gave a statistically significant increase in the risk of severe COVID-19 and an increase in mortality. At the same time, the analysis of real clinical practice data dictated the need to establish a number of restrictions on the use of certain classes of biologics and to search for alternative therapy programs to maintain control over disease activity. PURPOSE OF THE STUDY: The purpose of the study was to evaluate the efficacy and safety of the drug Artlegia® (olokizumab), solution for subcutaneous injection, 160 mg/ml-0.4 ml, manufactured by R-Pharm JSC, Russia) for the treatment of patients with rheumatoid arthritis in real clinical practice after switching with rituximab during the COVID-19 pandemic. MATERIALS AND METHODS: The study included 14 patients with a confirmed diagnosis of rheumatoid arthritis (RA), who were previously on rituximab therapy at a dose of 1000-500 mg twice with an interval of 2 weeks, who received at least one course of therapy with this drug. As RA worsened, patients were switched to olokizumab against the background of standard DMARDs. On weeks 0, 4, 8, and 12 after the switch, the severity of pain was assessed on the VAS scale, the number of tender and swollen joints (TJC28 and SJC28), the level of acute-phase inflammation markers, the DAS28 (disease activity score), ESR, CRP, CDAI (clinical activity index), and the functional state index HAQ (Health Assessment Questionnaire) were determined, as well as the safety profile of therapy was assessed. RESULTS: Data analysis was performed using median values (Me) were used for data analysis. A significant decrease in TJC28 was detected after 8 and 12 weeks of treatment with olokizumab (Artlegia®) (Me baseline = 10, Me 8 weeks = 4, Me 12 weeks = 4, p < 0.05) and a decrease in TSC28 was detected after 4, 8, and 12 weeks of treatment (Me baseline = 9, Me 4 weeks = 3.5, Me 8 weeks = 2.5, Me 12 weeks = 2.0, p < 0.05). Laboratory markers of inflammation showed a decrease in CRP and ESR levels after 4 weeks of treatment (CRP: Me4 weeks = 21, Me4 weeks = 1, p < 0.05, ESR: Mesno = 31, Me4 weeks = 7, p < 0.05). Positive dynamics persisted on 8 and 12 weeks (CRP: Me 8 weeks = 1, Me 12 weeks = 0; ESR: Me 8 weeks = 4, Me 12 weeks = 5). The level of CRP by week 4 became within the normal range, regardless of the initial values. All activity indices improved from week 4 in each evaluation period compared to baseline: DAS28-ESR: Me baseline = 5.52, Me 4 weeks = 3.59, Me 8 weeks = 3.33, Me 12 weeks = 3.22, p < 0.05; DAS28CRP: Me baseline = 5.39, Me 4 weeks = 3.71, Me 8 weeks = 3.35, Me 12 weeks = 3.45, p < 0.05; CDAI: Me baseline = 28.5, Me 4 weeks = 18.0, Me 8 weeks = 16.5, Me 12 weeks = 16.0, p < 0.05. All patients showed a reduction in pain (VAS scale) by week 8. The functional status of patients, according to the HAQ index, showed a significant decrease only by week 12 of the study: Me baseline = 1.62, Me 12 weeks = 1.31, p < 0.05. CONCLUSIONS: The study found that switching from rituximab to olokizumab was effective and safe during the COVID-19 pandemic.

Gene Therapies in Clinical Development to Treat Retinal Disorders.

Gene therapies have emerged as promising treatments in clinical development for various retinal disorders, offering hope to patients with inherited degenerative eye conditions. Several gene therapies have already shown remarkable success in clinical trials, with significant improvements observed in visual acuity and the preservation of retinal function. A multitude of gene therapies have now been delivered safely in human clinical trials for a wide range of inherited retinal disorders but there are some gaps in the reported trial data. Some of the most exciting treatment options are not under peer review and information is only available in press release form. Whilst many trials appear to have delivered good outcomes of safety, others have failed to meet primary endpoints and therefore not proceeded to phase III. Despite this, such trials have enabled researchers to learn how best to assess and monitor patient outcomes, which will guide future trials to greater success. In this review, we consider recent and ongoing clinical trials for a variety of potential retinal gene therapy treatments and discuss the positive and negative issues related to these trials. We discuss the treatment potential following clinical trials as well as the potential risks of some treatments under investigation. As these therapies continue to advance through rigorous testing and regulatory approval processes, they hold the potential to revolutionise the landscape of retinal disorder treatments, providing renewed vision and enhancing the quality of life for countless individuals worldwide.

Full-spectrum cannabidiol reduces UVB damage through the inhibition of TGF-ß1 and the NLRP3 inflammasome.

The thermodynamic characteristics, antioxidant potential, and photoprotective benefits of full-spectrum cannabidiol (FS-CBD) against UVB-induced cellular death were examined in this study. In silico analysis of CBD showed antioxidant capacity via proton donation and UV absorption at 209.09, 254.73, and 276.95 nm, according to the HAT and SPLET methodologies. FS-CBD protected against UVB-induced bacterial death for 30 min. FS-CBD protected against UVB-induced cell death by 42% (1.5 µg/mL) and 35% (3.5 µg/mL) in an in vitro keratinocyte cell model. An in vivo acute irradiated CD-1et/et mouse model (UVB-irradiated for 5 min) presented very low photoprotection when FS-CBD was applied cutaneously, as determined by histological analyses. In vivo skin samples showed that FS-CBD regulated inflammatory responses by inhibiting the inflammatory markers TGF-ß1 and NLRP3. The docking analysis showed that the CBD molecule had a high affinity for TGF-ß1 and NLRP3, indicating that protection against inflammation might be mediated by blocking these proinflammatory molecules. This result was corroborated by the docking interactions between CBD and TGF-ß1 and NLRP3, which resulted in a high affinity and inhibition of both proteins The present work suggested a FS-CBD moderate photoprotective agent against UVB light-induced skin damage and that this effect is partially mediated by its anti-inflammatory activity.

In-Vitro Study of the Binding of Atorvastatin with Adenine using Multi-Spectroscopic Approaches.

Atorvastatin-an oral lipid regulating drug is a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), which is the rate determining enzyme for cholesterol synthesis. Adenine is a purine nucleobase that is found in deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) to generate genetic information. The binding mechanism of atorvastatin and adenine was studied for the first time utilizing various techniques, including UV-visible spectrophotometry, spectrofluorimetry, synchronous fluorescence spectroscopy (SF), Fourier transform infrared (FTIR), fluorescence resonance energy transfer (FRET), and metal ion complexation. The fluorescence spectra of the complex indicated that atorvastatin is bound to adenine via hydrophobic interaction through a spontaneous binding process, and the fluorescence quenching mechanism was found to be static quenching with a binding constant of 1.4893 × 104 Lmol-1 at 298 K. Various temperature settings were used to investigate thermodynamic characteristics, such as binding forces, binding constants, and the number of binding sites. The interaction parameters, including the standard enthalpy change (ΔHο) and standard entropy change (ΔSο) were calculated using Van't Hoff's equation to be 42.82 kJmol-1 and 208.9 Jmol-1K-1, respectively. The findings demonstrated that the adenine- atorvastatin binding was endothermic. Furthermore, the results of the experiments revealed that some metal ions (K+, Ca+2, Co+2, Cu+2, and Al+3) facilitate the binding interaction between atorvastatin and adenine. Slight changes are observed in the FTIR spectra of adenine, indicating the binding interaction between adenine and atorvastatin.

Spatially limited pathogen pollution in an invasive tick and host system.

Expansion of global commerce has facilitated pathogen pollution via the transportation and translocation of invasive species and their associated parasites and pathogens. In Florida, imported cane toads (Rhinella horribilis) were accidentally and intentionally released on multiple occasions. Early populations were found to be infested with the invasive tick, Amblyomma rotundatum, yet it is unknown if these ticks dispersed with their hosts as cane toads spread throughout much of the state. The objectives of our investigation were to (1) determine if there are fewer tick infestations on toads at the periphery than at the core of their distribution as predicted by founder effect events, and (2) identify if ticks were infected with exotic pathogens. We captured toads from 10 populations across Florida. We collected ticks, vent tissue, and tick attachment site tissue from each toad, then tested samples for bacteria in the genus, Rickettsia. We found that 3/10 populations had toads that were infested with A. rotundatum, and infested individuals were in the earliest introduced populations at the core of their distribution. Pathogen testing confirmed Rickettisa bellii in ticks, but not in toad tissues. Haplotype networks could not clearly distinguish if R. bellii in Florida was more closely related to North or South American strains, but host-tick associations suggest that the pathogen was exotic to Florida. Our investigation demonstrated that an invasive species facilitated the introduction of parasites and pathogens into Florida, yet the invasive tick species encountered limitations to dispersal on this host species. Supplementary Information: The online version contains supplementary material available at 10.1007/s10530-024-03291-9.

Search for biocontrol agents among endophytic lipopeptide-synthesizing bacteria Bacillus spp. to protect wheat plants against Greenbug aphid (Schizaphis graminum).

Beneficial endophytic bacteria can suppress the development of insect pests through direct antagonism, with the help of metabolites, or indirectly by the induction of systemic resistance through the regulation of hormonal signaling pathways. Lipopeptides are bacterial metabolites that exhibit direct antagonistic activity against many organisms, including insects. Also, lipopeptides are able to trigger induced systemic resistance (ISR) in plants against harmful organisms, but the physiological mechanisms of their action are just beginning to be studied. In this work, we studied ten strains of bacteria isolated from the tissues of wheat and potatoes. Sequencing of the 16S rRNA gene showed that all isolates belong to the genus Bacillus and to two species, B. subtilis and B. velezensis. The genes for lipopeptide synthetase - surfactin synthetase (Bs_srf ), iturin synthetase (Bs_ituA, Bs_ituB) and fengycin synthetase (Bs_fenD) - were identified in all bacterial isolates using PCR. All strains had high aphicidal activity against the Greenbug aphid (Schizaphis graminum Rond.) due to the synthesis of lipopeptides, which was proven using lipopeptide-rich fractions (LRFs) isolated from the strains. Endophytic lipopeptide-synthesizing strains of Bacillus spp. indirectly affected the viability of aphids, the endurance of plants against aphids and triggered ISR in plants, which manifested itself in the regulation of oxidative metabolism and the accumulation of transcripts of the Pr1, Pr2, Pr3, Pr6 and Pr9 genes due to the synthesis of lipopeptides, which was proven using LRF isolated from three strains: B. subtilis 26D, B. subtilis 11VM, and B. thuringiensis B-6066. We have for the first time demonstrated the aphicidal effect of fengycin and the ability of the fengycin-synthesizing strains and isolates, B. subtilis Ttl2, Bacillus sp. Stl7 and B. thuringiensis B-6066, to regulate components of the pro-/antioxidant system of aphid-infested plants. In addition, this work is the first to demonstrate an elicitor role of fengycin in triggering a systemic resistance to S. graminum in wheat plants. We have discovered new promising strains and isolates of endophytes of the genus Bacillus, which may be included in the composition of new biocontrol agents against aphids. One of the criteria for searching for new bacteria active against phloem-feeding insects can be the presence of lipopeptide synthetase genes in the bacterial genome.

The performance of metabolomics-based prediction scores for mortality in older patients with solid tumors.

Prognostic information is needed to balance benefits and risks of cancer treatment in older patients. Metabolomics-based scores were previously developed to predict 5- and 10-year mortality (MetaboHealth) and biological age (MetaboAge). This study aims to investigate the association of MetaboHealth and MetaboAge with 1-year mortality in older patients with solid tumors, and to study their predictive value for mortality in addition to established clinical predictors. This prospective cohort study included patients aged ≥ 70 years with a solid malignant tumor, who underwent blood sampling and a geriatric assessment before treatment initiation. The outcome was all-cause 1-year mortality. Of the 192 patients, the median age was 77 years. With each SD increase of MetaboHealth, patients had a 2.32 times increased risk of mortality (HR 2.32, 95% CI 1.59-3.39). With each year increase in MetaboAge, there was a 4% increased risk of mortality (HR 1.04, 1.01-1.07). MetaboHealth and MetaboAge showed an AUC of 0.66 (0.56-0.75) and 0.60 (0.51-0.68) for mortality prediction accuracy, respectively. The AUC of a predictive model containing age, primary tumor site, distant metastasis, comorbidity, and malnutrition was 0.76 (0.68-0.83). Addition of MetaboHealth increased AUC to 0.80 (0.74-0.87) (p = 0.09) and AUC did not change with MetaboAge (0.76 (0.69-0.83) (p = 0.89)). Higher MetaboHealth and MetaboAge scores were associated with 1-year mortality. The addition of MetaboHealth to established clinical predictors only marginally improved mortality prediction in this cohort with various types of tumors. MetaboHealth may potentially improve identification of older patients vulnerable for adverse events, but numbers were too small for definitive conclusions. The TENT study is retrospectively registered at the Netherlands Trial Register (NTR), trial number NL8107. Date of registration: 22-10-2019.