RAINIER: A Simulation Tool for Distributions of Excited Nuclear States and Cascade Fluctuations

A new code has been developed named RAINIER that simulates the $\gamma$-ray decay of discrete and quasi-continuum nuclear levels for a user-specified range of energy, angular momentum, and parity including a realistic treatment of level spacing and transition width fluctuations. A similar program, DICEBOX, uses the Monte Carlo method to simulate level and width fluctuations but is restricted to $\gamma$-ray decay from no more than two initial states such as de-excitation following thermal neutron capture. On the other hand, modern reaction codes such as TALYS and EMPIRE populate a wide range of states in the residual nucleus prior to $\gamma$-ray decay, but do not go beyond the use of deterministic functions and therefore neglect cascade fluctuations. This combination of capabilities allows RAINIER to be used to determine quasi-continuum properties through comparison with experimental data. Several examples are given that demonstrate how cascade fluctuations influence experimental high-resolution $\gamma$-ray spectra from reactions that populate a wide range of initial states.Comment: 14 pages, 13 figures, Nuclear Instrumentation and Methods A, 201

An unusual presentation of pancreatic pseudocyst mimicking cystic neoplasm of the pancreas: a case report

In spite of their rarity, cystic neoplasms of the pancreas are characterized by existing or potential malignancy that cannot be ignored during decisive process with regard to the choice of treatment. Diagnostic difficulties in the differentiation of pancreatic pseudocyst and cystic pancreatic neoplasm can lead to misdiagnosis and inappropriate treatment, since clinical symptoms, preoperative imaging tests and even endoscopic retrograde cholangiopancreatography are often not sufficient to establish the correct diagnosis. We present a case of pancreatic cyst with no typical features of pseudocyst in the medical interview, treated by Child's subtotal pancreatectomy by reason of the high risk of neoplasia suggested by radiological and endoscopic examinations

Lipid Production From Waste Materials in Seawater-Based Medium by the Yeast Yarrowia lipolytica

The global limitation of fossil fuels impels scientists to search for new energy sources. A good alternative is biodiesel produced from crop plants. However, its production requires huge quantities of farmland, fertilizers and fresh water, which is in conflict with the human demand for water for consumption and land for food production. Thus, production of single cell oil (SCO) by oleaginous microorganisms remains the best solution for the coming years. Whereas most microorganisms require fresh water for proper cell metabolism, in this study we demonstrate that the unconventional yeast Yarrowia lipolytica is able to produce huge quantities of fatty acid in seawater-based medium. Here we shown that Y. lipolytica is able to produce fatty acids in medium based on seawater and crude glycerol as the main carbon source, which allows for low-cost production of SCO, is beneficial for industrial application and is ecologically friendly

Neratinib protects pancreatic beta cells in diabetes

The loss of functional insulin-producing β-cells is a hallmark of diabetes. Mammalian sterile 20-like kinase 1 (MST1) is a key regulator of pancreatic β-cell death and dysfunction; its deficiency restores functional β-cells and normoglycemia. The identification of MST1 inhibitors represents a promising approach for a β-cell-protective diabetes therapy. Here, we identify neratinib, an FDA-approved drug targeting HER2/EGFR dual kinases, as a potent MST1 inhibitor, which improves β-cell survival under multiple diabetogenic conditions in human islets and INS-1E cells. In a pre-clinical study, neratinib attenuates hyperglycemia and improves β-cell function, survival and β-cell mass in type 1 (streptozotocin) and type 2 (obese Leprdb/db) diabetic mouse models. In summary, neratinib is a previously unrecognized inhibitor of MST1 and represents a potential β-cell-protective drug with proof-of-concept in vitro in human islets and in vivo in rodent models of both type 1 and type 2 diabetes

Effectiveness and safety of PCSK9 inhibitor therapy in patients with familial hypercholesterolemia within a therapeutic program in Poland: Preliminary multicenter data

Background: In Poland, treatment with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors has become available free of charge in a therapeutic program. Assessed herein, is the efficacy and safety of alirocumab and evolocumab in patients with heterozygous familial hypercholesterolemia (FH).Methods: Data of 55 adult FH patients who participated in the program were analyzed upon meeting the criteria established by the Ministry of Health (low density lipoprotein cholesterol [LDL-C] above 160 mg/dL on max. tolerated statin dose and ezetimib). The efficacy of PCSK9 inhibitors in reducing LDL-C with drug administration every 2 weeks was assessed after 3 months and 1 year of therapy. A safety profile evaluation was performed at each visit. 48 patients completed the 3-month and 21 for the 1-year observation periods (34 patients treated with alirokumab and 14 with evolocumab).Results: The mean concentration of direct-measured LDL-C decreased from the initial level of 215.1 ± 74.5 mg/dL to 75.3 ± 64.1 mg/dL, i.e., by 65 ± 14% following 3 months of treatment. This effect was stable in 1-year observation (77.7 ± 72.8 mg/dL). Adverse effects were flu-like symptoms (13.0%), injection site reactions (11.1%), fatigue (5.6%) and musculoskeletal symptoms (5.6%). Seven patients failed to complete the 3-month treatment period due to side effects or non-compliance, and 1 patient failed to complete the 1-year treatment due to myalgia.Conclusions: This study confirmed high effectiveness of PCSK9 inhibitors in reducing LDL-C levels in patients with FH. Due to restrictive inclusion criteria with LDL-C threshold level > 160 mg/dL (> 4.1 mmol/L) required for participation in the therapeutic program, a relatively small number of FH patients were eligible for treatment

Out-of-hospital cardiac arrest: Do we have to perform coronary angiography?

Out-of-hospital cardiac arrest (OHCA) remains a leading cause of global mortality, while survivors are burdened with long-term neurological and cardiovascular complications. OHCA management at the hospital level remains challenging, due to heterogeneity of OHCA presentation, the critical status of OHCA patients reaching the return of spontaneous circulation (ROSC), and the demands of post ROSC treatment. The validity and optimal timing for coronary angiography is one important, yet not fully defined, component of OHCA management. Guidelines state clear recommendations for coronary angiography in OHCA patients with shockable rhythms, cardiogenic shock, or in patients with ST-segment elevation observed in electrocardiography after ROSC. However, there is no established consensus on the angiographic management in other clinical settings. While coronary angiography may accelerate the diagnostic and therapeutic process (provided OHCA was a consequence of coronary artery disease), it might come at the cost of impaired post-resuscitation care quality due to postponing of intensive care management. The aim of the current statement paper is to discuss clinical strategies for the management of OHCA including the stratification to invasive procedures and the rationale behind the risk-benefit ratio of coronary angiography, especially with patients in critical condition

Deep venous thrombosis due to massive compression by uterine myoma

A 42-year-old woman, gravida 3, para 3 was admitted to hospital because of painful oedema of her right lower extremity. Initial physical examination revealed a gross, firm tumour filling the entire peritoneal cavity. Doppler ultrasound scan revealed a thrombus in the right common iliac vein, extending to the right femur and popliteal veins, and partially into the calf deep vein. Computed tomography confirmed the existence of an abdominal tumour probably deriving from the genital organs and the presence of a thrombus in the said veins.The patient underwent hysterectomy where a myomatous uterine was removed. She was put on subcutaneous enoxaparine and compressive therapy of the lower extremities. Such symptoms as pain and oedema receded. Control Doppler scan showed fibrinolysis, partial organization of the thrombus and final vein recanalisation. After exclusion of other risk factors of deep vein thrombosis apart from stasis, we conclude that the described pathology was the effect of compression of regional pelvic structures by a uterine myoma

Rye and Oat Agricultural Wastes as Substrate Candidates for Biomass Production of the Non-Conventional Yeast Yarrowia lipolytica

The aim of this study was to test rye straw, rye bran and oat bran hydrolysates as substrates for growth of the yeast Yarrowia lipolytica, a microorganism known to have large biotechnological potential. First, after the combined process of acid-enzymatic hydrolysis, the concentration and composition of fermentable monosaccharides in the obtained hydrolysates were analyzed. Glucose was the main sugar, followed by xylose and arabinose. Rye bran hydrolysate had the highest sugar content—80.8 g/L. The results showed that this yeast was able to grow on low-cost medium and produce biomass that could be used as a feed in the form of single cell protein. The biomass of yeast grown in oat bran hydrolysate was over 9 g/L after 120 h, with the biomass total yield and total productivity values of 0.141 g/g and 0.078 g/h, respectively. The protein contents in yeast biomass were in the range of 30.5–44.5% of dry weight. Results obtained from Y. lipolytica cultivated in rye bran showed high content of exogenous amino acid (leucine 3.38 g, lysine 2.93 g, threonine 2.31 g/100 g of dry mass) and spectrum of unsaturated fatty acid with predominantly oleic acid—59.28%. In conclusion, these results demonstrate that lignocellulosic agricultural waste, after hydrolysis, could be efficiently converted to feed-related yeast biomass

Characterization of erythrose reductase from Yarrowia lipolytica and its influence on erythritol synthesis

Abstract Background Erythritol is a natural sweetener that is used in the food industry. It is produced as an osmoprotectant by bacteria and yeast. Due to its chemical properties, it does not change the insulin level in the blood, and therefore it can be safely used by diabetics. Previously, it has been shown that erythrose reductase (ER), which catalyzes the final step, plays a crucial role in erythritol synthesis. ER reduces erythrose to erythritol with NAD(P)H as a cofactor. Despite many studies on erythritol synthesis by Yarrowia lipolytica, the enzymes involved in this metabolic pathway have ever been described. Results The gene YALI0F18590g encoding the predicted erythrose reductase from Y. lipolytica was overexpressed, and its influence on erythritol synthesis was studied. The amino acid sequence of the Y. lipolytica ER showed a high degree of similarity to the previously described erythrose reductases from known erythritol producers, such as Candida magnoliae and Moniliella megachiliensis. Here, we found that the gene overexpression results in an enhanced titer of erythritol of 44.44 g/L (20% over the control), a yield of 0.44 g/g and productivity of 0.77 g/L/h. Moreover, on purification and characterization of the enzyme we found that it displays the highest activity at 37 °C and pH 3.0. The effects of various metal ions (Zn2+, Cu2+, Mn2+, Fe2+) on erythrose reductase were investigated. The addition of Zn2+ ions at 0.25 mM had a positive effect on the activity of erythrose reductase from Y. lipolytica, as well as on the erythritol production. Conclusions In this study we identified, overexpressed and characterized a native erythrose reductase in Y. lipolytica. Further optimizations of this strain via metabolic pathway engineering and media optimization strategies enabled 54 g/L to be produced in a shake-flask experiment. To date, this is the first reported study employing metabolic engineering of the native gene involved in the erythritol pathway to result in a high titer of the polyol. Moreover, it indicates the importance of environmental conditions for genetic targets in metabolic engineering

The Overexpression of YALI0B07117g Results in Enhanced Erythritol Synthesis from Glycerol by the Yeast Yarrowia lipolytica

The unconventional yeast Yarrowia lipolytica is used to produce erythritol from glycerol. In this study, the role of the erythrose reductase (ER) homolog YALI0B07117g in erythritol synthesis was analyzed. The deletion of the gene resulted in an increased production of mannitol (308%) and arabitol (204%) before the utilization of these polyols began. The strain overexpressing the YALI0B07117g gene was used to increase the erythritol yield from glycerol as a sole carbon source in batch cultures, resulting in a yield of 0.4 g/g. The specific consumption rate (qs) increased from 5.83 g/g/L for the WT strain to 8.49 g/g/L for the modified strain and the productivity of erythritol increased from 0.28 g/(L h) for the A101 strain to 0.41 g/(L h) for the modified strain. The application of the research may prove positive for shortening the cultivation time due to the increased rate of consumption of the substrate combined with the increased parameters of erythritol synthesis