Summary
Effective prevention of chronic postoperative pain is an important clinical goal, informed by a growing body of studies. Peri‐operative regional anaesthesia remains one of the most important ...tools in the multimodal analgesic toolbox, blocking injury‐induced activation and sensitisation of both the peripheral and central nervous system. We review the definition and taxonomy of chronic postoperative pain, its mechanistic basis and the most recent evidence for the preventative potential of multimodal analgesia, with a special focus on regional anaesthesia. While regional anaesthesia targets several important aspects of the mechanistic pathway leading to chronic postoperative pain, evidence for its efficacy is still mixed, possibly owing to the heterogeneity of risk profiles within the surgical patient, but also to variation in techniques and medications reported in the literature.
Nivolumab is approved as an option for third- or later-line treatment of advanced gastric/gastroesophageal junction (G/GEJ) cancer in several countries after ATTRACTION-2. To further improve the ...therapeutic efficacy of first-line therapy, exploration of a nivolumab-chemotherapy combination is warranted. In part 1 (phase II) of ATTRACTION-4, the safety and efficacy of nivolumab combined with S-1 plus oxaliplatin (SOX) or capecitabine plus oxaliplatin (CapeOX) as first-line therapy for unresectable advanced or recurrent human epidermal growth factor receptor 2 (HER2)-negative G/GEJ cancer were evaluated.
Patients were randomized (1 : 1) to receive nivolumab (360 mg intravenously every 3 weeks) plus SOX (S-1, 40 mg/m2 orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130 mg/m2 intravenously on day 1 every 3 weeks) or CapeOX (capecitabine, 1000 mg/m2 orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130 mg/m2 intravenously on day 1 every 3 weeks) until disease progression, unacceptable toxicity, or consent withdrawal.
Of 40 randomized patients, 39 (nivolumab plus SOX, 21; nivolumab plus CapeOX, 18) and 38 (21 and 17, respectively) comprised the safety and efficacy populations, respectively. Most frequent (>10%) grade 3/4 treatment-related adverse events were neutropenia (14.3%) in the nivolumab plus SOX group, and neutropenia (16.7%), anemia, peripheral sensory neuropathy, decreased appetite, type 1 diabetes mellitus, and nausea (11.1% each) in the nivolumab plus CapeOX group. No treatment-related death occurred. Objective response rate was 57.1% (95% confidence interval 34.0–78.2) with nivolumab plus SOX and 76.5% (50.1–93.2) with nivolumab plus CapeOX. Median overall survival was not reached (NR) in both groups. Median progression-free survival was 9.7 months (5.8–NR) and 10.6 months (5.6–12.5), respectively.
Nivolumab combined with SOX/CapeOX was well tolerated and demonstrated encouraging efficacy for unresectable advanced or recurrent HER2-negative G/GEJ cancer. ATTRACTION-4 has proceeded to part 2 (phase III) to compare nivolumab plus SOX/CapeOX versus placebo plus SOX/CapeOX.
NCT02746796.
Highly crystalline SnO2 is demonstrated to serve as a stable and robust electron‐transporting layer for high‐performance perovskite solar cells. Benefiting from its high crystallinity, the relatively ...thick SnO2 electron‐transporting layer (≈120 nm) provides a respectable electron‐transporting property to yield a promising power conversion efficiency (PCE)(18.8%) Over 90% of the initial PCE can be retained after 30 d storage in ambient with ≈70% relative humidity.
Low‐temperature, solution‐processable Cu‐doped NiOX (Cu:NiOx), prepared via combustion chemistry, is demonstrated as an excellent hole‐transporting layer (HTL) for thin‐film perovskite solar cells ...(PVSCs). Its good crystallinity, conductivity, and hole‐extraction properties enable the derived PVSC to have a high power conversion efficiency (PCE) of 17.74%. Its general applicability for various elecrode materials is also revealed.
Background
Obesity accelerates and exacerbates the age-related changes on muscle function and exercise capacity. In addition, the middle-aged population is often overlooked when talking about the ...prevention of sarcopenia. This study investigated the effects of exercise alone or in combination with a high-protein diet on muscle function and physical fitness in middle-aged obese adults.
Materials and methods
Sixty-nine middle-aged (501–64 years old) obese adults were randomly assigned to one of the following groups: control group (C; n=23), exercise group (E; n=23) or exercise plus high-protein group (EP; n=23). Individuals within the E and EP groups received 12 weeks of exercise training; whereas, the individuals in the EP group also received a highprotein diet intervention (1.6g/kg/day). Individuals within the C group were asked to maintain their lifestyle for 12 weeks. Participants were evaluated before and after the intervention. Outcome measures included maximal exercise capacity, muscle function and functional physical performance. Analysis of covariance was used to determine the effects of the intervention.
Results
After the intervention, the E and EP groups had greater maximal work rate, peak oxygen consumption, and muscle power during muscle contractions at 180°/sec than that in the C group (P<0.05). The EP group, but not the E group, showed significant improvement in the sit-to-stand test and climbing stairs test than the C group after the intervention (P<0.05). Within group comparisons showed that the anaerobic threshold only increased in the EP group (+12% from pre-test).
Conclusions
For middle-aged obese adults, exercise with a high-protein diet not only improved muscle power and exercise capacity but also enhanced their functional physical performance.
The recent advent of transition‐metal mediated CH activation is revolutionizing the synthetic field and gradually infusing a “CH activation mind‐set” in both students and practitioners of organic ...synthesis. As a powerful testament of this emerging synthetic tool, applications of CH activation in the context of total synthesis of complex natural products are beginning to blossom. Herein, recently completed total syntheses showcasing creative and ingenious incorporation of CH activation as a strategic manoeuver are compared with their “non‐CH activation” counterparts, illuminating a new paradigm in strategic synthetic design.
The total synthesis of natural products has been carried out showcasing the creative and ingenious application of CH activation in the construction of complex molecular architectures that are compared with their “non‐CH activation” counterparts. These accomplishments stood as true testaments of the growing potential of CH activation, and further cementing the power of this emerging synthetic technology (see figure).
In this tutorial review, recent advances in the synthesis of cyclopropane-containing natural products are discussed, highlighting the application of novel synthetic methodologies and innovative ...synthetic strategies in the construction of highly functionalized cyclopropanes. The examples showcased herein aim to inspire students and practitioners of organic synthesis to seek further advances in the chemical synthesis of cyclopropanes, both in the context of target-oriented syntheses and method developments.
In this review article, recent advances in the total synthesis of cyclopropane-containing natural products are highlighted.
Vascular endothelial growth factor (VEGF) has a central role in breast cancer development and progression, but the mechanisms that control its expression are poorly understood. Breast cancer tissue ...microarrays revealed an inverse correlation between the Forkhead transcription factor Forkhead box class O (FOXO)3a and VEGF expression. Using the lapatinib-sensitive breast cancer cell lines BT474 and SKBR3 as model systems, we tested the possibility that VEGF expression is negatively regulated by FOXO3a. Lapatinib treatment of BT474 or SKBR3 cells resulted in nuclear translocation and activation of FOXO3a, followed by a reduction in VEGF expression. Transient transfection and inducible expression experiments showed that FOXO3a represses the proximal VEGF promoter, whereas another Forkhead member, FOXM1, induces VEGF expression. Chromatin immunoprecipitation and oligonucleotide pull-down assays showed that both FOXO3a and FOXM1 bind a consensus Forkhead response element (FHRE) in the VEGF promoter. Upon lapatinib stimulation, activated FOXO3a displaces FOXM1 bound to the FHRE before recruiting histone deacetylase 2 (HDAC2) to the promoter, leading to decreased histones H3 and H4 acetylation, and concomitant transcriptional inhibition of VEGF. These results show that FOXO3a-dependent repression of target genes in breast cancer cells, such as VEGF, involves competitive displacement of DNA-bound FOXM1 and active recruitment of transcriptional repressor complexes.
A low‐bandgap (1.33 eV) Sn‐based MA0.5FA0.5Pb0.75Sn0.25I3 perovskite is developed via combined compositional, process, and interfacial engineering. It can deliver a high power conversion efficiency ...(PCE) of 14.19%. Finally, a four‐terminal all‐perovskite tandem solar cell is demonstrated by combining this low‐bandgap cell with a semitransparent MAPbI3 cell to achieve a high efficiency of 19.08%.
PDF
