Liver transplantation in the critically ill: donation after cardiac death compared to donation after brain death grafts

Patients with end stage liver disease may become critically ill prior to LT requiring admission to the intensive care unit (ICU). The high acuity patients may be thought too ill to transplant; however, often LT is the only therapeutic option. Choosing the correct liver allograft for these patients is often difficult and it is imperative that the allograft work immediately. Donation after cardiac death (DCD) donors provide an important source of livers, however, DCD graft allocation remains a controversial topic, in critically ill patients. Between January 2003-December 2008, 1215 LTs were performed: 85 patients at the time of LT were in the ICU. Twelve patients received DCD grafts and 73 received donation after brain dead (DBD) grafts. After retransplant cases and multiorgan transplants were excluded, 8 recipients of DCD grafts and 42 recipients of DBD grafts were included in this study. Post-transplant outcomes of DCD and DBD liver grafts were compared. While there were differences in graft and survival between DCD and DBD groups at 4 month and 1 year time points, the differences did not reach statistical significance. The graft and patient survival rates were similar among the groups at 3-year time point. There is need for other large liver transplant programs to report their outcomes using liver grafts from DCD and DBD donors. We believe that the experience of the surgical, medical and critical care team is important for successfully using DCD grafts for critically ill patients.     

Synthesis and insight into the structure–activity relationships of 2-phenylbenzimidazoles as prospective anticancer agents

In order to explore and develop new anticancer agents, three series of 2-phenylbenzimidazoles, 15–46, were condensed under simple and mild conditions using sodium metabisulfite as an oxidation agent and another series, 47–55, were obtained via a reduction reaction using sodium borohydride. All the compounds synthesized were evaluated for their in vitro anticancer activities against three human cancer cell lines. The novel compound 38 was found to be the most potent multi cancer inhibitor against A549, MDA-MB-231, and PC3 cell lines (IC₅₀ values 4.47, 4.68 and 5.50 μg mL⁻¹, respectively). In addition, compound 40 exhibited the best IC₅₀ value of 3.55 μg mL⁻¹ against the MDA-MB-231 cell line. The results demonstrated that introducing a new substituent to compounds 37–55 could improve their antiproliferative activities.

Three series of 2-phenylbenzimidazoles obtained under simple and convenient pathways, were used to elucidate their SARs against three cancer cell lines: A549, MDA-MB-231 and PC3.     

Controlled synthesis of ultrathin MoS2 nanoflowers for highly enhanced NO2 sensing at room temperature

Fabrication of a high-performance room-temperature (RT) gas sensor is important for the future integration of sensors into smart, portable and Internet-of-Things (IoT)-based devices. Herein, we developed a NO₂ gas sensor based on ultrathin MoS₂ nanoflowers with high sensitivity at RT. The MoS₂ flower-like nanostructures were synthesised via a simple hydrothermal method with different growth times of 24, 36, 48, and 60 h. The synthesised MoS₂ nanoflowers were subsequently characterised by scanning electron microscopy, X-ray diffraction, Raman spectroscopy, energy-dispersive X-ray spectroscopy and transmission electron microscopy. The petal-like nanosheets in pure MoS₂ agglomerated to form a flower-like structure with Raman vibrational modes at 378 and 403 cm⁻¹ and crystallisation in the hexagonal phase. The specific surface areas of the MoS₂ grown at different times were measured by using the Brunauer–Emmett–Teller method. The largest specific surface area of 56.57 m² g⁻¹ was obtained for the MoS₂ nanoflowers grown for 48 h. This sample also possessed the smallest activation energy of 0.08 eV. The gas-sensing characteristics of sensors based on the synthesised MoS₂ nanostructures were investigated using oxidising and reducing gases, such as NO₂, SO₂, H₂, CH₄, CO and NH₃, at different concentrations and at working temperatures ranging from RT to 150 °C. The sensor based on the MoS₂ nanoflowers grown for 48 h showed a high gas response of 67.4% and high selectivity to 10 ppm NO₂ at RT. This finding can be ascribed to the synergistic effects of largest specific surface area, smallest crystallite size and lowest activation energy of the MoS₂-48 h sample among the samples. The sensors also exhibited a relative humidity-independent sensing characteristic at RT and a low detection limit of 84 ppb, thereby allowing their practical application to portable IoT-based devices.

Controlled synthesis of ultrathin MoS₂ nanoflowers is crucial to develop a high-performance room-temperature NO₂ gas sensor for the future integration of sensors into smart, portable and Internet-of-Things (IoT)-based devices.     

API ionic liquids: probing the effect of counterion structure on physical form and lipid solubility

Lipid based formulations (LBFs) are extensively utilised as an enabling technology in drug delivery. The use of ionic liquids (ILs) or lipophilic salts (LS) in drug delivery has also garnered considerable interest due to unique solubility properties. Conversion of active pharmaceutical ingredients (API) to ILs by pairing with an appropriately lipophilic counterion has been shown to decrease melting point of the salt complex and improve solubility in LBFs. However, the relationship between the structure of the counterion, the physicochemical properties of the resulting salts and solubility in LBFs has not been systematically explored. This study investigates the relationship between alkyl sulfate counterion structure and melting temperature (T_m or T_g) in addition to LBF solubility, utilizing cinnarizine and lumefantrine as model weakly basic APIs. Three series of structurally diverse alkyl sulfate counterions were chosen to probe this relationship. Pairing cinnarizine and lumefantrine with a majority of these alkyl sulfate counterions resulted in a reduction in melting temperature and enhanced solubility in model medium chain and long chain LBFs. The chain length of the alkyl sulfate plays a crucial role in performance, and consistently branched alkyl sulfate counterions perform better than straight chain alkyl sulfate counterions, as predicted. Most interestingly, trends in counterion performance were found to be consistent across two APIs with disparate chemical structures. The findings from this study will facilitate the design of counterions which enhance solubility of ionisable drugs and unlock the potential to develop compounds previously restrained by poor solubility.

Structure/property relationship of API IL counterions and salt physicochemical properties are investigated, the results highlight the complex interplay involved.     

Functionalization of C–H bonds in acetophenone oximes with arylacetic acids and elemental sulfur

Fused thieno[3,2-d]thiazoles were synthesized via a coupling of acetophenone ketoximes, arylacetic acids, and elemental sulfur in the presence of Li₂CO₃ base. Functionalities including chloro, bromo, fluoro, trifluoromethyl, and pyridyl groups were compatible with reaction conditions. High yields and excellent regioselectivities were obtained even if meta-substituted ketoxime acetates were used. Ethyl esters of heteroarylacetic acids were competent substrates, which is very rare in the literature. Our method would offer a convenient protocol to afford polyheterocyclic structures from simple substrates.

Annulation of acetophenone oxime acetates, arylacetic acids or esters, and elemental sulfur in absence of transition metals is reported.     

Electrodeposited nickel–graphene nanocomposite coating: effect of graphene nanoplatelet size on its microstructure and hardness

In this study, the effect of graphene nanoplatelet (GNP) size on the microstructure and hardness of the electrodeposited nickel–graphene nanocomposite coatings were investigated. GNPs with different sizes were prepared by using a high energy ball milling technique. The experimental result revealed the high energy ball milling technique could reduce the size, increase the surface area, and improve the dispersion ability of GNPs. The microstructure, hardness, and components of the nanocomposite coatings were greatly affected by GNP sizes. The highest microhardness was measured to be 273 HV for the nanocomposite coatings containing 5 h-milled GNPs, which is increased up to ∼47% compared to pristine Ni coating. The enhancement in the hardness is attributed to the uniform dispersion of the small GNP sizes inside the Ni matrix and the Ni grain size reduction when using milled GNPs.

The effect of graphene nanoplatelet size on the microstructure and hardness of electrodeposited nickel–graphene nanocomposite coatings was investigated.     

Quantitative ultrasound and fracture risk prediction in non-osteoporotic men and women as defined by WHO criteria

Summary

This study sought to determine the association between calcaneal quantitative ultrasound (QUS) and fracture risk in individuals without osteoporosis according to the World Health Organization criteria (i.e., BMD T-score?>??2.5). We found that calcaneal QUS is an independent predictor of fracture risk in women with non-osteoporotic bone mineral density (BMD).

Introduction

More than 50 % of women and 70 % of men who sustain a fragility fracture have BMD above the osteoporotic threshold (T-score?>??2.5). Calcaneal QUS is associated with fracture risk. This study aimed to test the hypothesis that low calcaneal QUS is associated with increased fracture risk in individuals with non-osteoporotic BMD.

Methods

We included 312 women and 390 men aged 62–90 years with BMD T-score?>??2.5 at femoral neck. QUS was measured in broadband ultrasound attenuation (BUA) at the calcaneus using a CUBA sonometer. BMD was measured at the femoral neck (FNBMD) by dual energy X-ray absorptiometry using GE Lunar DPX-L densitometer. The incidences of any fragility fracture were ascertained by X-ray reports during the follow-up period from 1994 to 2011.

Results

Of the 702 participants, 26 % of women (n?=?80/312) and 14 % of men (n?=?53/390) experienced at least one fragility fracture during the follow-up period. In women, after adjusting for covariates, increased risk of any fracture was significantly associated with decreased BUA (HR?=?1.50; 95 % CI, 1.13–1.99). Compared with that of FNBMD, the models with BUA, in women, had greater AUC (0.71, 0.85, 0.71 for any, hip and vertebral fracture, respectively), and yielded a net reclassification improvement of 16.4 % (P?=?0.009) when combined with FNBMD. In men, BUA was not significantly associated with fracture risk before and after adjustment.

Conclusion

These results suggest that calcaneal BUA is an independent predictor of fracture risk in women with non-osteoporotic BMD.     

Evolution of Glycolipid Profile After Sleeve Gastrectomy vs. Roux-en-Y Gastric Bypass: Results of a Prospective Randomized Clinical Trial

Background

This study aims to report glycolipid changes after sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) in the setting of a prospective randomized clinical trial.

Methods

One hundred patients were randomly assigned to RYGB (n?=?45) and SG (n?=?55). Fasting glucose, insulin, glycated hemoglobin (HbA1c%), triglycerides, and serum cholesterol (total, HDL, and LDL) were evaluated at inclusion and after 1, 3, 6, and 12 months. The index for homeostasis model assessment of insulin resistance (HOMA-IR) and β cell function (HOMA-B) were assessed.

Results

Mean postoperative 1-, 3-, 6-, and 12-month excess weight loss was 25.39, 43.47, 63.75, and 80.38 % after RYGB and 25.25, 51.32, 64.67, and 82.97 % after SG, respectively. Mean fasting glucose and fasting serum insulin were similarly and statistically significantly reduced in both RYGB and SG. Mean HOMA-IR improved in both groups, particularly in case of high preoperative values, and mean HOMA-B improved at 1 year after RYGB. HbA1c% dropped from 5.66 % (SD?=?0.61) to 5.57 % (SD?=?0.32) after RYGB and from 5.64 % (SD?=?0.43) to 5.44 % (SD?=?0.43) after SG. Total cholesterol was significantly higher at 1 month (p?=?0.04), 3 months (p?=?0.03), and 1 year (p?=?0.005) after SG as compared to RYGB. LDL cholesterol decreased significantly after RYGB at 1 month (p?=?0.03), 3 months (p?=?0.0001), and 1 year (p?=?0.0004) as compared to SG. HDL cholesterol was increased at 1 year in the RYGB group but not in the SG group. Triglycerides decreased similarly in both groups.

Conclusions

Short-term glycemic control was comparable after SG and RYGB. An improved lipid profile was noted after RYGB in patients with abnormal preoperative values.