Chirality is a fundamental symmetry property; chiral objects, such as chiral small molecules, exist as a pair of non-superimposable mirror images. Although small-molecule chirality is routinely ...considered in biologically focused application areas (such as drug discovery and chemical biology), other areas of scientific development have not considered small-molecule chirality to be central to their approach. In this Review, we highlight recent research in which chirality has enabled advancement in technological applications. We showcase examples in which the presence of small-molecule chirality is exploited in ways beyond the simple interaction of two different chiral molecules; this can enable the detection and emission of chiral light, help to control molecular motion, or provide a means to control electron spin and bulk charge transport. Thus, we demonstrate that small-molecule chirality is a highly promising avenue for a wide range of technologically oriented scientific endeavours.Although it is a fundamental property of many small molecules, chirality is not widely exploited in materials applications as its benefits are not widely recognized — indeed, the need for stereoselective synthesis may be seen as a disadvantage. In this Review, we highlight recent research in which chirality has had an enabling impact in technological applications.
The emission of circularly polarized light is central to many applications, including data storage, optical quantum computation, biosensing, environmental monitoring, and display technologies. An ...emerging method to induce (chiral) circularly polarized (CP) electroluminescence from the active layer of polymer light-emitting diodes (polymer OLEDs; PLEDs) involves blending achiral polymers with chiral small-molecule additives, where the handedness/sign of the CP light is controlled by the absolute stereochemistry of the small molecule. Through the in-depth study of such a system we report an interesting chiroptical property: the ability to tune the sign of CP light as a function of active layer thickness for a fixed enantiomer of the chiral additive. We demonstrate that it is possible to achieve both efficient (4.0 cd/A) and bright (8000 cd/m2) CP-PLEDs, with high dissymmetry of emission of both left-handed (LH) and right-handed (RH) light, depending on thickness (thin films, 110 nm: g EL = 0.51, thick films, 160 nm: g EL = −1.05, with the terms “thick” and “thin” representing the upper and lower limits of the thickness regime studied), for the same additive enantiomer. We propose that this arises due to an interplay between localized CP emission originating from molecular chirality and CP light amplification or inversion through a chiral medium. We link morphological, spectroscopic, and electronic characterization in thin films and devices with theoretical studies in an effort to determine the factors that underpin these observations. Through the control of active layer thickness and device architecture, this study provides insights into the mechanisms that result in CP luminescence and high performance from CP-PLEDs, as well as demonstrating new opportunities in CP photonic device design.
Abstract
Hepatorenal syndrome (HRS) is a serious complication of end-stage liver disease, occurring mainly in patients with advanced cirrhosis and ascites, who have marked circulatory dysfunction,1 ...as well as in patients with acute liver failure.2 In spite of its functional nature, HRS is associated with a poor prognosis,3 4 and the only effective treatment is liver transplantation.
During the 56th Meeting of the American Association for the Study of Liver Diseases, the International Ascites Club held a Focused Study Group (FSG) on HRS for the purpose of reporting the results of an international workshop and to reach a consensus on a new definition, criteria for diagnosis and recommendations on HRS treatment. A similar workshop was held in Chicago in 1994 in which standardised nomenclature and diagnostic criteria for refractory ascites and HRS were established.5 The introduction of innovative treatments and improvements in our understanding of the pathogenesis of HRS during the previous decade led to an increasing need to undertake a new consensus meeting. This paper reports the scientific rationale behind the new definitions and recommendations.
The international workshop included four issues debated by four panels of experts (see Acknowledgements). The issues were: (1) evidence-based HRS pathogenesis; (2) treatment of HRS using vasoconstrictors; (3) other HRS treatments using transjugular intrahepatic portosystemic stent-shunt (TIPS) and extracorporeal albumin dialysis (ECAD); and (4) new definitions and diagnostic criteria for HRS and recommendations for its treatment.
Hepatorenal syndrome (HRS), a serious complication of cirrhosis, is associated with high mortality without treatment. Terlipressin with albumin is effective in the reversal of HRS. Where terlipressin ...is not available, as in the United States, midodrine and octreotide with albumin are used as an alternative treatment of HRS. The aim was to compare the effectiveness of terlipressin plus albumin versus midodrine and octreotide plus albumin in the treatment of HRS in a randomized controlled trial. Twenty‐seven patients were randomized to receive terlipressin with albumin (TERLI group) and 22 to receive midodrine and octreotide plus albumin (MID/OCT group). The TERLI group received terlipressin by intravenous infusion, initially 3 mg/24 hours, progressively increased to 12 mg/24 hours if there was no response. The MID/OCT group received midodrine orally at an initial dose of 7.5 mg thrice daily, with the dose increased to a maximum of 12.5 mg thrice daily, together with octreotide subcutaneously: initial dose 100 μg thrice daily and up to 200 μg thrice daily. Both groups received albumin intravenously 1 g/kg of body weight on day 1 and 20‐40 g/day thereafter. There was a significantly higher rate of recovery of renal function in the TERLI group (19/27, 70.4%) compared to the MID/OCT group (6/21, 28.6%), P = 0.01. Improvement in renal function and lower baseline Model for End‐Stage Liver Disease score were associated with better survival. Conclusion: Terlipressin plus albumin is significantly more effective than midodrine and octreotide plus albumin in improving renal function in patients with HRS (Hepatology 2015;62:567–574
Background & Aims: Several randomized controlled trials have compared a transjugular intrahepatic portosystemic shunt (TIPS) with large-volume paracentesis in cirrhotic patients with refractory ...ascites. Although all agree that TIPS reduces the recurrence rate of ascites, survival is controversial. The aim of this study was to compare the effects of TIPS and large-volume paracentesis in cirrhotic patients with refractory ascites by means of meta-analysis of individual patient data from 4 randomized controlled trials. Methods: The study population consisted of 305 patients: 149 allocated to TIPS and 156 to paracentesis. Cumulative probabilities of transplant-free survival and of hepatic encephalopathy (HE) were estimated by the Kaplan–Meier method and differences assessed by log-rank test. The total number of HE episodes per patient was also compared between TIPS and paracentesis. Results: Tense ascites recurred in 42% of patients allocated to TIPS and 89% allocated to paracentesis ( P < .0001). Sixty-five patients in the TIPS group and 78 in the paracentesis group died. The actuarial probability of transplant-free survival was significantly better in the TIPS group ( P = .035). Cox regression analysis performed in a subgroup of 235 patients (114 allocated to TIPS and 121 to paracentesis) showed that age, serum bilirubin level, plasma sodium level, and treatment allocation were independently associated with transplant-free survival. The average number of HE episodes was significantly higher in the TIPS group (1.13 ± 1.93 vs 0.63 ± 1.18; P = .006), although the cumulative probability of developing the first episode of HE was similar between the groups ( P = .19). Conclusions: The present meta-analysis of individual patient data provides further evidence to the previous meta-analyses of literature data showing that TIPS significantly improves transplant-free survival of cirrhotic patients with refractory ascites.
Polymer thin films that emit and absorb circularly polarised light have been demonstrated with the promise of achieving important technological advances; from efficient, high-performance displays, to ...3D imaging and all-organic spintronic devices. However, the origin of the large chiroptical effects in such films has, until now, remained elusive. We investigate the emergence of such phenomena in achiral polymers blended with a chiral small-molecule additive (1-aza6helicene) and intrinsically chiral-sidechain polymers using a combination of spectroscopic methods and structural probes. We show that - under conditions relevant for device fabrication - the large chiroptical effects are caused by magneto-electric coupling (natural optical activity), not structural chirality as previously assumed, and may occur because of local order in a cylinder blue phase-type organisation. This disruptive mechanistic insight into chiral polymer thin films will offer new approaches towards chiroptical materials development after almost three decades of research in this area.
Clear cell renal cell carcinoma (ccRCC) has a poor prognosis despite novel biological targeted therapies. Tumor aggressiveness and poor survival may correlate with tumor grade at diagnosis and with ...complex metabolic alterations, also involving glucose and lipid metabolism. However, currently no grade-specific metabolic therapy addresses these alterations. Here we used primary cell cultures from ccRCC of low- and high-grade to investigate the effect on energy state and reduced pyridine nucleotide level, and on viability and proliferation, of specific inhibition of glycolysis with 2-deoxy-D-glucose (2DG), or fatty acid oxidation with Etomoxir. Our primary cultures retained the tissue grade-dependent modulation of lipid and glycogen storage and aerobic glycolysis (Warburg effect). 2DG affected lactate production, energy state and reduced pyridine nucleotide level in high-grade ccRCC cultures, but the energy state only in low-grade. Rather, Etomoxir affected energy state in high-grade and reduced pyridine nucleotide level in low-grade cultures. Energy state and reduced pyridine nucleotide level were evaluated by ATP and reduced 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) dye quantification, respectively. 2DG treatment impaired cell proliferation and viability of low-grade ccRCC and normal cortex cultures, whereas Etomoxir showed a cytostatic and cytotoxic effect only in high-grade ccRCC cultures. Our data indicate that in ccRCC the Warburg effect is a grade-dependent feature, and fatty acid oxidation can be activated for different grade-dependent metabolic needs. A possible grade-dependent metabolic therapeutic approach in ccRCC is also highlighted.
Purposes
We evaluated the prevalence and factors associated with polypharmacy and investigated the role of polypharmacy as a predictor of length of hospital stay and in-hospital mortality.
Methods
...Thirty-eight internal medicine wards in Italy participated in the
Re
gistro
Po
literapie
SI
MI (REPOSI) study during 2008. One thousand three hundred and thirty-two in-patients aged ≥65 years were enrolled. Polypharmacy was defined as the concomitant use of five or more medications. Linear regression analyses were used to evaluate predictors of length of hospital stay and logistic regression models for predictors of in-hospital mortality. Age, sex, Charlson comorbidity index, polypharmacy, and number of in-hospital clinical adverse events (AEs) were used as possible confounders.
Results
The prevalence of polypharmacy was 51.9% at hospital admission and 67.0% at discharge. Age, number of drugs at admission, hypertension, ischemic heart disease, heart failure, and chronic obstructive pulmonary disease were independently associated with polypharmacy at discharge. In multivariate analysis, the occurrence of at least one AE while in hospital was the only predictor of prolonged hospitalization (each new AE prolonged hospital stay by 3.57 days,
p
< 0.0001). Age odds ratio (OR) 1.04; 95% confidence interval (CI) 1.01–1.08;
p
= 0.02), comorbidities (OR 1.18; 95% CI 1.12–1.24;
p
< 0.0001), and AEs (OR 6.80; 95% CI 3.58–12.9;
p
< 0.0001) were significantly associated with in-hospital mortality.
Conclusions
Although most elderly in-patients receive polypharmacy, in this study, it was not associated with any hospital outcome. However, AEs were strongly correlated with a longer hospital stay and higher mortality risk.
Interstitial lung diseases (ILDs) are a heterogeneous group of diseases characterized by widespread fibrotic and inflammatory abnormalities of the lung. Respiratory failure is a common complication ...in advanced stages or following acute worsening of the underlying disease. Aim of this review is to evaluate the current evidence in determining the best management of acute respiratory failure (ARF) in ILDs.
A literature search was performed in the Medline/PubMed and EMBASE databases to identify studies that investigated the management of ARF in ILDs (the last search was conducted on November 2017).
In managing ARF, it is important to establish an adequate diagnostic and therapeutic management depending on whether the patient has an underlying known chronic ILD or ARF is presenting in an unknown or de novo ILD. In the first case both primary causes, such as acute exacerbations of the disease, and secondary causes, including concomitant pulmonary infections, fluid overload and pulmonary embolism need to be investigated. In the second case, a diagnostic work-up that includes investigations in regards to ILD etiology, such as autoimmune screening and bronchoalveolar lavage, should be performed, and possible concomitant causes of ARF have to be ruled out. Oxygen supplementation and ventilatory support need to be titrated according to the severity of ARF and patients' therapeutic options. High-Flow Nasal oxygen might potentially be an alternative to conventional oxygen therapy in patients requiring both high flows and high oxygen concentrations to correct hypoxemia and control dyspnea, however the evidence is still scarce. Neither Non-Invasive Ventilation (NIV) nor Invasive Mechanical Ventilation (IMV) seem to change the poor outcomes associated to advanced stages of ILDs. However, in selected patients, such as those with less severe ARF, a NIV trial might help in the early recognition of NIV-responder patients, who may present a better short-term prognosis. More invasive techniques, including IMV and Extracorporeal Membrane Oxygenation, should be limited to patients listed for lung transplant or with reversible causes of ARF.
Despite the overall poor prognosis of ARF in ILDs, a personalized approach may positively influence patients' management, possibly leading to improved outcomes. However, further studies are warranted.
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