New Insights on the Relationship between Leptin, Ghrelin, and Leptin/Ghrelin Ratio Enforced by Body Mass Index in Obesity and Diabetes

Currently, adipose tissue is considered an endocrine organ, however, there are still many questions regarding the roles of adipokines—leptin and ghrelin being two adipokines. The purpose of the study was to assess the relationship between the adipokines and their ratio with obesity and diabetes. Methods: Sixty patients (mean age 61.88 ± 10.08) were evaluated. Cardiovascular risk factors, leptin, ghrelin, and insulin resistance score values were assessed. The patients were classified according to their body mass index (BMI) as normal weight, overweight, and obese. Results: 20% normal weight, 51.7% overweight, 28.3% obese, and 23.3% diabetic. Obese patients had higher leptin values (in obese 34,360 pg/mL vs. overweight 18,000 pg/mL vs. normal weight 14,350 pg/mL, p = 0.0049) and leptin/ghrelin ratio (1055 ± 641 vs. 771.36 ± 921 vs. 370.7 ± 257, p = 0.0228). Stratifying the analyses according to the presence of obesity and patients’ gender, differences were found for leptin (p = 0.0020 in women, p = 0.0055 in men) and leptin/ghrelin ratio (p = 0.048 in women, p = 0.004 in men). Mean leptin/BMI and leptin/ghrelin/BMI ratios were significantly higher, and the ghrelin/BMI ratio was significantly lower in obese and diabetic patients. In conclusion, obesity and diabetes are associated with changes not only in the total amount but also in the level of adipokines/kg/m2. Changes appear even in overweight subjects, offering a basis for early intervention in diabetic and obese patients.

Temperament Trait Changes in Japanese Black Cows Under Grazing and Confined Conditions

The objective of the present study was to reveal the effects of grazing on the temperament traits of cows. Nine Japanese Black cows [344 ± 32 kg body weight (BW), 7.7 ± 3.0 year of age], which had various experiences, such as tethering, handling, and grazing, were used in this experiment. Five of the nine cows were grazed for 3 months on a 1.8-ha field composed of a sown pasture with forestland. The remaining cows were fed in confinement. On days 38, 52, 72, and 86 after the start of grazing, the temperament traits observed in various situations, such as moving to the body weight scale, weighing, handling, moving to the stock for blood sampling, holding in the stock, and obtaining a blood sample, were assessed with a visual analog scale (VAS: 1–10) or score (1–5). During weighing and handling, the intensity of resistance exhibited by the grazing cows, as evaluated by head movement, walking/stepping, tail flicking, rope tension, and overall movement, was lower than that exhibited by confined cows (P < 0.05). The resistance score exhibited by the grazing cows during blood sampling was also lower than that exhibited by confined cows (P < 0.01). These results suggest that grazing enhances docility in cows with various experiences in different situations encountered in daily management.

Cross-species identification of cancer-resistance associated genes uncovers their relevance to human cancer risk

Cancer is an evolutionarily conserved disease that occurs in a wide variety of species. We applied a comparative genomics approach to systematically characterize the genes whose conservation levels significantly correlates positively (PC) or negatively (NC) with a broad spectrum of cancer-resistance estimates, computed across almost 200 vertebrate species. PC genes are enriched in pathways relevant to tumor suppression including cell cycle, DNA repair, and immune response, while NC genes are enriched with a host of metabolic pathways. The conservation levels of the PC and NC genes in a species serve to build the first genomics-based predictor of its cancer resistance score. We find that PC genes are less tolerant to loss of function (LoF) mutations, are enriched in cancer driver genes and are associated with germline mutations that increase human cancer risk. Furthermore, their expression levels are associated with lifetime cancer risk across human tissues. Finally, their knockout in mice results in increased cancer incidence. In sum, we find that many genes associated with cancer resistance across species are implicated in human cancers, pointing to several additional candidate genes that may have a functional role in human cancer.

Agroecological sustainability of varieties of regular bean to adverse vegetation conditions

Actuality of theme. Insignificant sown area and low yield of common bean seeds do not meet consumer needs for its products in Ukraine. One of the important factors in increasing the sown area and increasing the yield of beans is the correct selection of its varieties, taking into account their agri-environmental resistance to diseases, pests, drought and potential productivity. Goal. Therefore, the aim of our research was to analyze the available range of beans in terms of productivity and resistance to adverse environmental factors. Methods. Studies on the assessment of agroecological resistance of common bean varieties to adverse growing conditions were conducted on the basis of the State Register of Plant Varieties Suitable for Distribution in Ukraine for 2021, Official Descriptions of Plant Varieties and Economic Suitability Indicators submitted in the Official Bulletins, covered in the Information-reference system "Variety", as well as on the materials of scientific research Bezugla O.M., Ovcharuk O.V., Mazur O.V., Palamarchuk V.D., Klisha A.I., Kulinich O.O., Korzh Z.V., Olifirovich S.E., where the indicators of productivity of varieties of common beans are presented. Materials were analyzed by varieties of common beans (grain) and common beans (vegetables). The resistance of bean varieties to pests, diseases and drought was considered as unfavorable growing conditions. The relative resistance of plant varieties to adverse factors is established on a nine-point scale (1 – 9 points), in which 9 points corresponds to the highest resistance, and 1 point – the lowest resistance. Potential yield levels of seeds of grain beans and green beans of vegetable beans were also analyzed. We compared the studied indicators using mathematical-statistical correlation-regression analysis. Results. Common beans (grain) in the State Register of Plant Varieties Ukraine for 2021 is represented by 30 varieties. According to the level of potential seed yield, according to the State Register of Plant Varieties of Ukraine, among the varieties of grain beans predominate Eureka, Igolomskaya – 3.0 t/ha, Ros, Mavka – 2.80 t/ha, Yasochka – 2.78 t/ha, Nata – 2.75 t/ha, Shchedra, Assol, Slavia, Wawel – 2.70 t/ha each. The lowest declared seed yield of grain varieties Fresano, Pervomaiskaya, Dokuchaevskaya – 1.50 t/ha, Gaidarskaya, Dvadesyatitsa – 1.70 t/ha. The relative resistance of most varieties of common beans to the disease complex is determined by a score of 7 on a nine-point scale. Only the Gothic variety had the highest resistance to a complex of diseases – 9 points, the Otrada variety had a resistance score of 6, Dokuchaevskaya – 5, Pervomaiskaya – 4 points. Information on the resistance of grain varieties to pests in the State Register of Varieties is only partially written out. According to this document, the varieties Gaidarska, Gothic, Onyx, Perlina, Mavka and Nadiya have a resistance score of 7. There is no information on the resistance to pests of other varieties of grain beans in the document. The highest drought resistance, according to the State Register of varieties, has beans of the Wawel variety – 9 points, Igolomskaya, Zagadka, Dvadesyatitsa – 8 points each. The least drought-resistant varieties are Pervomaisk – 4 points, Veselka, Yarynka, Dokuchaevska – 5 points each. Most varieties of grain beans are characterized by an average score of drought resistance – 7. The State Register of Plant Varieties of Ukraine for 2021 presents 34 varieties of vegetable beans. The highest potential seed yield, according to the State Register of Plant Varieties of Ukraine, are varieties of vegetable beans Gina, Festival – 2.20 t/ha, Konza – 2.10 t/ha and Dolphin – 2.00 t/ha. The lowest seed yield is typical for Croquet varieties – 0.65 t/ha and Pike – 0.70 t/ha. Similar to grain beans, most varieties of vegetable beans have a disease resistance score of 7. Only the Nagano variety has a score of 8, Olga – 6, Festival, Faiza, Festin – 5 points each. Increased resistance to pests are varieties of beans vegetable Festival and Faiza, with a score of 8. For other varieties, information on their resistance to pests is missing. Vegetable varieties of vegetables Dolphin, Nagano, Shahinya, Croquet and Festin have the highest drought resistance – 8 points each. The least drought-resistant are Teroma – 5 points and Faiza – 6 points. Comparison of the potential seed yield of grain and vegetable varieties revealed an excess of the average yield of grain varieties by 37.2% compared to vegetables. Disease resistance in grain and vegetable beans is the same – 6.8 points each, and resistance to pests in vegetable beans is 12.5% higher than in grain beans. Drought resistance of vegetable varieties is 6.9% higher than grain beans. Conclusions. Among the varieties of grain beans according to the State Register of Plant Varieties of Ukraine for 2021 the highest potential seed yields are: Eureka, Igolomskaya, Ros, Mavka, Yasochka, Nata, Shchedra, Assol, Slavia, Wawel. The most drought-resistant varieties are Wawel, Igolom, Zagadka; to diseases - Gothic. Among the varieties of vegetable beans, the highest potential seed yields are: Gina, Festival, Konza and Delfina; green beans – Festival, Faiza and Festin. Nagano was the most resistant to diseases; to the influence of pests - Festival and Faiza; The most drought-resistant, according to the State Register of Plant Varieties of Ukraine for 2021, are the varieties Dolphin, Nagano, Shahinya, Croquet and Festin.

Metabolomic profiling of pancreatic adenocarcinoma reveals fundamental clinical features

In this study, we perform the metabolomics profiling of 77 PDAC patient-derived tumor xenografts (PDTX) to investigate the relationship of metabolic profiles with overall survival (OS) in PDAC patients, tumor phenotypes and resistance to five anticancer drugs (gemcitabine, oxaliplatin, docetaxel, SN-38 and 5-Fluorouracil). We identified a metabolic signature that was able to predict the clinical outcome of PDAC patients (p < 0.001, HR=2.68 [95% CI: 1.5-4.9]). The correlation analysis showed that this metabolomic signature was significantly correlated with the PDAC molecular gradient (PAMG) (R = 0.44 and p < 0.001) indicating significant association to the transcriptomic phenotypes of tumors. Resistance score established, based on growth rate inhibition metrics using 35 PDTX-derived primary cells, allowed to identify several metabolites related to drug resistance which was globally accompanied by accumulation of several diacy-phospholipids and decrease in lysophospholipids. Interestingly, targeting glycerophospholipid synthesis improved sensitivity to the three tested cytotoxic drugs indicating that interfering with metabolism could be a promising therapeutic strategy to overcome the challenging resistance of PDAC.Short abstractTargeting metabolism of cancer cells gives a precious opportunity to overcome challenges related to the high mortality and chemoresistance in PDAC.Metabolic profiling of PDAC patient-derived tumor xenografts used in this study allowed highlighting the strong link between metabolism and both clinical outcome of the patients and chemoresistance.Metabolic signature was able to discriminate between good and bad prognosis groups of patients based on their level of key metabolites.Identification of key metabolic markers associated to chemoresistance allowed to improve sensitivity to anticancer drugs.These results provide new insights to help to predict patient survival and elaborate new combinatory therapies against chemoresistance in PDAC patients attesting of the important clinical value of this work.

COMPARISON OF SUBLINGUAL MISOPROSTOLAND PER VAGINAL MISOPROSTOL FOR PAIN RELIEF DURING AND AFTER HSG PROCEDURE: A RANDOMIZED CONTROLLED TRIAL

Background: Misoprostol has been extensively used in obstetrics and has proved to be a very effective cervical softening agent before termination of pregnancy. The beneficial effects on cervical ripening may make misoprostol a desirable agent for helping cervical dilatation on non pregnant women. Aim: To compare the efficacy and safety of pre-procedure sublingual misoprostol versus pervaginal misoprostol for relief of pain during and after the HSG procedure. Materials and methods: Study was initiated after approval from the IEC. There after subject recruitment had done form July 2017 to June 2018 in the department of Obstetrics & Gynaecology (indoor setting) of IPGME&R & SSKM Hospital Result: We found that association of cervical resistance score vas vs. group was statistically significant (p<0.0001). Association of need for analgesics vs. group was not statistically significant (p=0.11004). Association of any adverse effect vs. group was not statistically significant (p=1.0000). Difference of mean age vs. group was not statistically significant (p=0.0717). Conclusion: There was no significant difference of pain after the HSG procedure in both the group. The patients who were received sublingual misoprostol had significantly low cervical resistance during the procedure.

Lipoprotein distribution of Apo CIII glycoforms in healthy men is linked with low TG and increased insulin sensitivity

ABSTRACTGlycosylation of Apo CIII modulates its function in triglyceride metabolism, and some variants are associated with a protective or pro-atherogenic lipid profile. These associations have been studied in whole plasma Apo CIII proteoforms, but the proportion of Apo CIII proteoforms in individual lipoprotein fractions has been rarely evaluated. In the present study, we aim to measure the relative content of Apo CIII proteoforms in each lipoprotein fraction (VLDL, IDL, LDL and HDL) in a group of healthy subjects as a potential biomarker for triglyceride metabolism, cardiovascular risk and diabetes. Lipoprotein fractions were separated by differential ultracentrifugation of plasma samples. The relative concentrations of seven Apo CIII variants were measured by mass spectrometric immunoassay, and the complete lipoprotein profile was determined by NMR. The results showed high interindividual variability in the distribution of Apo CIII proteoforms across the study population but a uniform proportion in all lipoprotein fractions. Two Apo CIII variants, Apo CIII0b and Apo CIII1d, were negatively correlated with plasma and VLDL triglycerides regardless of VLDL size and were associated with increased LDL size when transported in LDL particles. Apo CIII0b also showed a negative correlation with lipoprotein-insulin resistance score. Therefore, Apo CIII variants can be reliably measured in lipoprotein fractions, and our results suggest that Apo CIII0b and Apo CIII1d have a protective role in triglyceride metabolism and insulin resistance in healthy individuals.

Construction of a risk prediction model for subsequent bloodstream infection in intestinal carriers of carbapenem-resistant Enterobacteriaceae: a retrospective study in hematology department and intensive care unit

Background To establish a risk prediction model for carbapenem-resistant Enterobacteriaceae (CRE) bloodstream infection (BSI) in intestinal carriers. Methods CRE screenings were performed every two weeks in hematology department and intensive care unit (ICU). Patients with positive CRE rectal swab screening were identified using electronic healthcare records from 15 May 2018 to 31 December 2019. All CRE strains were collected and identified. Carriers who developed CRE BSI were compared with those who did not develop CRE infection. The control group 1:1 stratified randomly matched the case group. Univariate logistic analysis, multivariate logistic analysis and stepwise regression analysis were carried out. Results A total of 42 cases were included. Multivariate analysis showed that gastrointestinal injury (OR 86.82, 95%CI 2.58-2916.59, P = 0.013), tigecycline exposure (OR 14.99, 95%CI 1.82-123.74 P = 0.012) and carbapenem resistance score (OR 11.24, 95% CI 1.81–69.70, P = 0.009) were independent risk factors for CRE BSI in intestinal carriers (P < 0.05). They were included in the Logistic regression model to predict BSI. According to receiver operating characteristic (ROC) curve analysis, the cut-off value of the model was 0.72, and the sensitivity, specificity and area under the curve (AUC) were 90.5%, 85.7% and 0.92, respectively. Conclusions The risk prediction model based on gastrointestinal injury, tigecycline exposure and carbapenem resistance score of colonizing strain can effectively predict CRE BSI in patients with CRE colonization. Early CRE screening and detection for inpatients in key departments may early warning and reduce the risk of nosocomial infection of CRE.