Nevin Manimala

Histol Histopathol. 2021 Sep 30:18377. doi: 10.14670/HH-18-377. Online ahead of print.

ABSTRACT

Postpartum uterine diseases are associated with significant imbalance in the levels of biogenic amines (BAs) in rat uterus. Mast cells (MCs) are the main suppliers of BAs such as serotonin, catecholamines, and histamine in uterus. There is limited evidence of the BA-positive elements involved in the physiological regulation of uterus during postpartum involution. The aim of present study is to determine the concentration and distribution of biogenic amines (BAs) such as histamine, serotonin, and catecholamines in the uterine endometrium, myometrium, and peritoneal fluid (PF) during the postpartum uterine involution. A total of 110 nulliparous outbred female nonpregnant Wistar rats of mature age were divided into eleven groups (n=10 per group) according to days of postpartum involution. Tissue specimens of uterine segments, PF were prepared. Serotonin, catecholamines, and histamine concentrations were examined by fluorescence-histochemical techniques. The fluorescence of the BA-positive elements was detected and analyzed by microspectrofluorimetry. Results were analyzed using the Kruskal-Wallis chi-squared test and pairwise Mann-Whitney-Wilcoxon tests with “Benjamini-Hochberg correction” in R 3.6.3. Mast cells in uterine segments, PF exhibited characteristic yellowish-green fluorescence. The highest MCs number was reported in corpus uteri on the 15ᵗᵸ day of postpartum involution. Serotonin, catecholamines, and histamine levels were significantly higher in BA-positive elements in the initial days. BA content was dynamic and relies on the time elapsed after parturition. There was statistically significant difference in the levels of BAs in the cornu and cervix uteri. A single morphofunctional complex of BA supply was noticed in the reproductive system of the rats. The coupled interactions of intra- and extra-organic BA-positive elements was associated with anabolic/catabolic equilibrium in uterus through the metabolism of serotonin, catecholamines, and histamine during postpartum involution.

PMID:34590705 | DOI:10.14670/HH-18-377

J Biomech Eng. 2021 Sep 30. doi: 10.1115/1.4052577. Online ahead of print.

ABSTRACT

The characterization of human subcutaneous adipose tissue (SAT) under high-rate loading is valuable for development of biofidelic finite element human body models (FE-HBMs) to predict seat belt-pelvis interaction and injury risk in vehicle crash simulations. While material characterization of SAT has been performed at 25°C or 37°C, the effect of temperature on mechanical properties of SAT under high-rate and large-deformation loading has not been investigated. Similarly, while freezing is the most common preservation technique for cadaveric specimens, the effect of freeze-thaw on the mechanical properties of SAT is also absent from the literature. Therefore, the aim of this study was to determine the effect of freezing and temperature on mechanical properties of human SAT. Fresh and previously frozen human SAT specimens were obtained and tested at 25°C and 37°C. High-rate indentation and puncture tests were performed, and indentation-puncture force-depth responses were obtained. While the chance of material failure was found to be different between temperatures and between fresh and previously frozen tissue, statistical analyses revealed that temperature and freezing did not change the shear modulus and failure characteristics of SAT. Therefore, the results of the current study indicated that SAT material properties characterized from either fresh or frozen tissue at either 25°C or 37°C could be used for enhancing the biofidelity of FE-HBMs.

PMID:34590691 | DOI:10.1115/1.4052577

Hum Mol Genet. 2021 Sep 30:ddab279. doi: 10.1093/hmg/ddab279. Online ahead of print.

ABSTRACT

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key player in lipid metabolism, as it degrades LDL receptors from hepatic cell membranes. So far, only variants of the PCSK9 gene locus were found to be associated with PCSK9 levels. Here we aimed to identify novel genetic loci that regulate PCSK9 levels and how they relate to other lipid traits. Additionally, we investigated to what extend the causal effect of PCSK9 on coronary artery disease (CAD) is mediated by LDL-C.

METHODS & RESULTS: We performed a genome-wide association study meta-analysis of PCSK9 levels in up to 12,721 samples of European ancestry. The estimated heritability was 10.3%, which increased to 12.6% using only samples from patients without statin treatment. We successfully replicated the known PCSK9 hit consisting of three independent signals. Interestingly, in a study of 300 African Americans, we confirmed the locus with a different PCSK9 variant. Beyond PCSK9, our meta-analysis detected three novel loci with genome-wide significance. Co-localization analysis with cis-eQTLs and lipid traits revealed biologically plausible candidate genes at two of them: APOB and TM6SF2. In a bivariate Mendelian Randomization analysis, we detected a strong effect of PCSK9 on LDL-C, but not vice versa. LDL-C mediated 63% of the total causal effect of PCSK9 on CAD.

CONCLUSION: Our study identified novel genetic loci with plausible candidate genes affecting PCSK9 levels. Ethnic heterogeneity was observed at the PCSK9 locus itself. While the causal effect of PCSK9 on CAD is mainly mediated by LDL-C, an independent direct effect also occurs.

PMID:34590679 | DOI:10.1093/hmg/ddab279

Hum Mol Genet. 2021 Sep 30:ddab287. doi: 10.1093/hmg/ddab287. Online ahead of print.

ABSTRACT

OBJECTIVES: Epidemic obesity is the most important risk factor for prediabetes and type 2 diabetes (T2D) in youth as it is in adults. Obesity shares pathophysiological mechanisms with T2D and is likely to share part of the genetic background. We aimed to test if weighted genetic risk scores (GRSs) for T2D, fasting glucose (FG) and fasting insulin (FI) predict glycaemic traits and if there is a causal relationship between obesity and impaired glucose metabolism in children and adolescents.

DESIGN AND PATIENTS: Genotyping of 42 SNPs established by genome-wide association studies for T2D, FG and FI was performed in 1660 Italian youths aged between 2 and 19 years. We defined GRS for T2D, FG and FI and tested their effects on glycaemic traits, including FG, FI, indices of insulin resistance/beta cell function, and body mass index (BMI). We evaluated causal relationships between obesity and FG/FI using one-sample Mendelian Randomization analyses in both directions.

RESULTS: GRS-FG associated with FG (beta = 0.075 mmol/l, SE = 0.011, P = 1.58 × 10-11) and beta cell function (beta = -0.041, SE = 0.0090 P = 5.13 × 10-6). GRS-T2D also demonstrated an association with beta cell function (beta = -0.020, SE = 0.021 P = 0.030). We detected a causal effect of increased BMI on levels of FI in Italian youths (beta = 0.31 ln (pmol/l), 95%CI [0.078, 0.54], P = 0.0085), while there was no effect of FG/FI levels on BMI.

CONCLUSION: Our results demonstrate that the glycaemic and T2D risk genetic variants contribute to higher FG and FI levels and decreased beta cell function in children and adolescents. The causal effects of adiposity on increased insulin resistance are detectable from childhood age.

PMID:34590674 | DOI:10.1093/hmg/ddab287

Phys Chem Chem Phys. 2021 Sep 30. doi: 10.1039/d1cp03178c. Online ahead of print.

ABSTRACT

A statistical mechanical deconvolution procedure for the experimentally measured surface pressure-area isotherms has been presented to obtain the surface pressure dependence of the liquid expanded (LE) and liquid condensed (LC) nanocluster size distributions in the LE-LC phase coexistence region of the first order phase transition of Dimyristoyl phosphatidylcholine (DMPC) monolayers at the air-water interface. This study presents the application of the deconvolution formulation introduced originally by Freire and Biltonen for the experimentally measured specific heat to calculate the submicroscopic lipid cluster distribution function in the phase coexistence region [E. Freire, R. L. Biltonen, Biopolymers, 1978, 17, 481-496] and extends their formulation to surface pressure isotherms. The present procedure involves the extraction of the pressure partition function calculated from the isotherm and utilizes the general relation between molecular density fluctuations and macroscopic lateral compressibility. In this procedure the high-density LC phase boundary has been determined uniquely. The average nanoscopic cluster sizes obtained in this study have been compared with the results from previous experimental studies. The cause of the finite difference between the values of the LC phase boundary area obtained from the present deconvolution procedure and the conventional extrapolation method on the same isotherm has been discussed from the viewpoint of slow hierarchical growth from nanoscopic clusters to macroscopic domains in the coexistence region.

PMID:34590663 | DOI:10.1039/d1cp03178c

Anal Methods. 2021 Sep 30. doi: 10.1039/d1ay01212f. Online ahead of print.

ABSTRACT

Food additives are chemicals added to enhance the appearance, taste, or lifetime of food products. Authorities continuously update the lists of the allowed additives and their daily intake limits. Thus, authorities and food suppliers strictly monitor additives in food products to guarantee their safety and compliance with national laws and safety criteria. The daily intake of the food colorant sunset yellow is banned in some countries and strictly controlled in others. Herein, a chemically modified solid-state potentiometric sensor was fabricated and used for the direct, fast, sensitive and selective assay of sunset yellow in soft drink and pharmaceutical formulation samples. The study optimized the sensor composition and the optimized carbon paste included a novel polymeric ion-exchanger, dioctyl phthalate, chitosan, and calix-[8]-arene and produced a rapid and near-Nernstian response of -32.9 ± 0.821 mV per decade for sunset yellow in the concentration range 7.94 × 10^-5 M to 1.0 × 10^-2 M and in the pH range 5-10. The sensor revealed good selectivity toward sunset yellow in the presence of commonly encountered ionic species. The method was validated according to the International Council for Harmonization guidelines and the results were statistically comparable to those of a reported method. The solid-state sensor represents a tool for fast and direct assay of sunset yellow in food products without sample pretreatment.

PMID:34590633 | DOI:10.1039/d1ay01212f

Curr Oncol. 2021 Sep 21;28(5):3668-3682. doi: 10.3390/curroncol28050313.

ABSTRACT

BACKGROUND: Ovarian carcinoma (OC) is usually diagnosed at an advanced stage, necessitating a multimodal approach that includes surgery and systemic therapy. The incidence of OC is approximately five times higher in women over 65 years of age. Cardiovascular comorbidities and type 2 diabetes mellitus, both prevalent at this age, can influence therapeutic strategy and have an adverse effect on survival.

OBJECTIVES: Our study aimed to determine the impact of cardiovascular diseases and diabetes mellitus on survival in advanced ovarian cancer.

MATERIALS AND METHODS: From 2004 to 2012, we retrospectively studied 104 patients with advanced epithelial ovarian cancer (FIGO stage II-IV) who underwent surgical treatment at the Gynecology Clinic, St. Anna University Hospital, Varna, Bulgaria. Patients were followed for an average of 90 (52-129) months. We divided the study population into two groups: those with concurrent cardiovascular diseases and type 2 diabetes mellitus (CVD) and those without these comorbidities (No-CVD group). Overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were compared between groups using Kaplan-Meier survival analysis. Cardiovascular comorbidities and diabetes mellitus were evaluated for their prognostic value for survival using multivariate Cox proportional regression analysis adjusted for age, stage of OC, grade and histological type of the tumor, ascites presence, residual tumor size (RT), performance status, and type of hysterectomy.

RESULTS: The Kaplan-Meier analysis showed reduced OS and DSS in the CVD group compared to the No-CVD group. The median OS was 24.5 months (95% CI 18.38 months) and 38 months (95% CI 26, not reached), respectively (Log-rank p = 0.045). The median DSS was 25.5 months (95% CI 19.39 months) and 48 months (95% CI 28, not reached), respectively (Log-rank p = 0.033). The Cox regression multivariate analysis established a lower (by 68%) overall survival rate for the CVD patient group than the No-CVD group, approaching statistical significance (HR 1.68, 95% CI 0.99, 2.86, p = 0.055). Cardiovascular diseases and diabetes were associated with a 79% reduction in DSS (HR 1.79, 95% CI 1.02, 3.13, p = 0.041) and a twofold increase in the risk of disease progression (HR 2.05, 95% CI 1.25, 3.37, p = 0.005).

CONCLUSIONS: According to our study, cardiovascular comorbidities and diabetes may adversely affect OC survival. Optimal control of cardiovascular diseases, diabetes mellitus, and their risk factors may be beneficial for patients with advanced OC. Further research involving a larger patient population is necessary to establish these comorbidities as independent prognostic factors.

PMID:34590605 | DOI:10.3390/curroncol28050313

Curr Oncol. 2021 Aug 27;28(5):3323-3330. doi: 10.3390/curroncol28050288.

ABSTRACT

BACKGROUND: In our department, we provided guidelines to the radiation oncologists (ROs) regarding the omission, delay, or shortening of radiotherapy (RT). The purpose was to reduce the patients’ exposure to the hospital environment and to minimize the departmental overcrowding. The aim was to evaluate the ROs’ compliance to these guidelines.

METHODS: ROs were asked to fill out a data collection form during patients’ first visits in May and June 2020. The collected data included the ROs’ age and gender, patient age and residence, RT purpose, treated tumor, the dose and fractionation that would have been prescribed, and RT changes. The chi-square test and binomial logistic regression were used to analyze the correlation between the treatment prescription and the collected parameters.

RESULTS: One hundred and twenty-six out of 205 prescribed treatments were included in this analysis. Treatment was modified in 61.1% of cases. More specifically, the treatment was omitted, delayed, or shortened in 7.9, 15.9, and 37.3% of patients, respectively. The number of delivered fractions was reduced by 27.9%. A statistically significant correlation (p = 0.028) between younger patients’ age and lower treatment modifications rate was recorded.

CONCLUSION: Our analysis showed a reasonably high compliance of ROs to the pandemic-adapted guidelines. The adopted strategy was effective in reducing the number of admissions to our department.

PMID:34590595 | DOI:10.3390/curroncol28050288

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2021 Aug;33(8):973-978. doi: 10.3760/cma.j.cn121430-20200917-00633.

ABSTRACT

OBJECTIVE: To investigate the correlation between the level of serum 25-hydroxyvitamin D [25(OH)D] and infarction volume in patients with acute ischemic stroke (AIS) with internal carotid artery system (anterior circulation).

METHODS: A prospective cohort study was conducted. Patients with AIS admitted to the department of emergency of Beijing Boai Hospital from October 2017 to September 2019 were enrolled. Nutritional risk screening 2002 (NRS 2002) were assessed in all cases within 24 hours after enrollment. Fasting venous blood was collected for biochemical analysis, including albumin (ALB), homocysteine (HCY), uric acid (UA), hypersensitive C-reactive protein (hs-CRP), etc. Serum 25(OH)D level was detected by electrochemiluminescence immunoassay. Magnetic resonance imaging (MRI) was performed to calculate the volume of cerebral infarction. According to the volume of cerebral infarction, the patients were divided into small volume (≤ 1 cm³) group, medium volume (1 cm³ < infarct volume < 20 cm³) group and large volume (≥ 20 cm³) group. The differences of serum 25(OH)D and other indicators in each group were compared; the influencing factors of infarct volume were analyzed by Logistic regression; and the goodness of fit of regression model was tested by Hosmer-Lemeshow (HL).

RESULTS: A total of 224 patients with AIS were enrolled, 92 in small volume group, 90 in medium volume group and 42 in large volume group, and there was no significant difference in serum 25(OH)D level among small, medium and large volume groups [μg/L: 13.21 (7.47, 19.33), 11.20 (7.00, 15.07), 9.19 (6.30, 17.10), H = 4.994, P = 0.082]. There were 124 patients with AIS in anterior circulation, 45, 56 and 23 patients in the small, medium and large volume groups, respectively, with the increase of the cerebral infarction volume, the serum 25(OH)D level in small, medium and large volume groups decreased gradually, and the difference was statistically significant [μg/L: 13.22 (9.00, 19.65), 10.41 (6.72, 14.92), 8.30 (4.70, 11.30), H = 11.068, P = 0.004]. In addition, with the increase of the cerebral infarction volume, the older the patients with AIS in anterior circulation [years old: 63.0 (54.0, 75.5), 76.0 (63.0, 84.0), 82.0 (67.5, 85.0), H = 14.981, P = 0.001], the higher the nutritional risk ratio (35.6%, 53.6%, 73.9%, χ² = 9.271, P = 0.010), the higher the serum hs-CRP level [mg/L: 1.91 (0.92, 3.40), 4.10 (1.73, 22.42), 19.74 (4.02, 68.81), H = 21.477, P < 0.001], and the lower the ALB level (g/L: 42.30±12, 38.11±5.06, 35.14±5.49, F = 19.347, P < 0.001). After adjusting for age, gender, atrial fibrillation, nutritional risk, hs-CRP and other confounding factors, serum 25(OH)D was an independent protective factor for the infarct volume of AIS in anterior circulation [odds ratio (OR) = 0.962, P = 0.040], For every 10 μg/L decrease of 25(OH)D, the risk of one grade increase in infarction volume was increased by 47.7% respectively (goodness of fit: χ² = 5.357, P = 0.719).

CONCLUSIONS: The low serum 25(OH)D level was associated with the increase of infarct volume in the anterior circulation cerebral infarction, and early detection of serum 25(OH)D level can help risk stratification of AIS patients.

PMID:34590566 | DOI:10.3760/cma.j.cn121430-20200917-00633

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2021 Aug;33(8):944-948. doi: 10.3760/cma.j.cn121430-20201231-00790.

ABSTRACT

OBJECTIVE: To observe the effects of self-made Qingyuan Shenghua decoction on coagulation dysfunction in patients with sepsis, and to explore its possible mechanism.

METHODS: Eighty patients with sepsis and coagulation dysfunction admitted to the department of critical care medicine of Chengdu First People’s Hospital from March 2018 to April 2020 were enrolled. The patients were divided into control group and observation group according to random number table method, with 40 cases in each group. Patients in both groups received basic treatment for sepsis. On this basis, the observation group was administrated with self-made Qingyuan Shenghua decoction, one dose a day, 100 mL in the morning and 100 mL in the evening; the control group was given the same amount of normal saline. Both groups were treated for 7 days. Prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR), fibrinogen (Fib), D-dimer, platelet count (PLT), white blood cell count (WBC), C-reactive protein (CRP), and procalcitonin (PCT) were measured before and after treatment, and acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) were calculated. The length of intensive care unit (ICU) stay, the incidence of multiple organ dysfunction syndrome (MODS) and 28-day mortality was recorded.

RESULTS: The indexes of coagulation function and inflammation in the two groups were significantly improved after treatment, the improvement of various indexes in the observation group were better than those in the control group [PT (s): 16.01±1.08 vs. 19.21±1.38, APTT (s): 55.33±15.29 vs. 79.41±12.69, INR: 1.30±0.21 vs. 1.65±0.22, Fib (g/L): 2.87±0.89 vs. 5.44±1.13, D-dimer (mg/L): 2.56±1.67 vs. 6.41±2.42, PLT (×10⁹/L): 125.79±18.51 vs. 95.46±18.50, WBC (×10⁹/L): 7.50±0.78 vs. 12.75±4.09, CRP (mg/L): 21.27±9.32 vs. 65.44±13.40, PCT (μg/L): 1.15±0.58 vs. 6.31±1.29], and the differences were statistically significant (all P < 0.05). After treatment, APACHE II and SOFA scores in the two groups decreased significantly compared with those before treatment, and the decrease in the observation group were more obvious than those in the control group (APACHE II score: 10.29±1.86 vs. 15.35±2.06, SOFA score: 5.51±1.08 vs. 7.65±1.58, both P < 0.05). The length of ICU stay was shortened in the observation group than that in the control group (days: 12.22±9.48 vs. 20.22±15.35, P < 0.05). The incidence of MODS [35.0% (14/40) vs. 47.5% (19/40)] and the 28-day mortality [45.0% (18/40) vs. 47.5% (19/40)] was lower than that of the control group, but there was no statistical difference (both P > 0.05).

CONCLUSIONS: Self-made Qingyuan Shenghua decoction can effectively improve the prognosis of patients with coagulation dysfunction and sepsis, and its mechanism may be related to inhibition of inflammatory reaction and improvement of coagulation function.

PMID:34590561 | DOI:10.3760/cma.j.cn121430-20201231-00790