Potentially inappropriate prescribing of cardiovascular system and antiplatelet/anticoagulant drugs among elderly patients:a Korean population-based national study

OBJECTIVES To investigate the prevalence of potentially inappropriate prescribing(PIP)for cardiovascular system(CVS)and antiplatelet/anticoagulant(AP/AC)drugs among Korean elderly patients,using the Screening Tool of Older Persons’Prescriptions(STOPP)criteria version 2 and to identify the risk factors related to PIP.METHODS The 2016 National Aged Patient Sample data,comprising National Health Insurance claim records for a random sample of 20%of patients aged≥65 years,were used to calculate PIP prevalence of outpatient prescriptions.For criteria including drugdisease interactions,PIP prevalence per indication was estimated.RESULTS Among 1,274,148 elderly patients and 27,062,307 outpatient prescription claims,100,085 patients(7.85%)and 341,664 claims(1.27%)had one or more PIP.The most frequent PIP was“nonsteroidal antiinflammatory drug with concurrent antiplatelet agent(s)without protonpump inhibitor prophylaxis”in the claimlevel(0.97%)and patientlevel(6.33%)analyses.“Betablocker with bradycardia”(16.47%of claims)and“angiotensin receptor blockers in patients with hyperkalaemia”(23.89%of claims)showed the highest PIP prevalence per indication.Logistic regression analysis revealed that,among the patient and health care provider characteristics,female,older age,more severe comorbidities,polypharmacy,higher level of healthcare organization,and specialty of prescriber were significantly associated with a higher risk of PIP.CONCLUSIONS Our findings of a high prevalence of PIP for CVS and AP/AC drugs among the elderly suggest that an effective strategy is urgently needed to improve the prescription practices of these drugs.

Terpenoids as potential chemopreventive and therapeutic agents in liver cancer

Despite significant advances in medicine, liver cancer, predominantly hepatocellular carcinoma remains a major cause of death in the United States as well as the rest of the world. As limited treatment options are currently available to patients with liver cancer, novel preventive control and effective therapeutic approaches are considered to be reasonable and decisive measures to combat this disease. Several naturally occurring dietary and non-dietary phytochemicals have shown enormous potential in the prevention and treatment of several cancers, especially those of the gastrointestinal tract. Terpenoids, the largest group of phytochemicals, traditionally used for medicinal purposes in India and China, are currently being explored as anticancer agents in clinical trials. Terpenoids (also called "isoprenoids") are secondary metabolites occurring in most organisms, particularly plants. More than 40 000 individual terpenoids are known to exist in nature with new compounds being discovered every year. A large number of terpenoids exhibit cytotoxicity against a variety of tumor cells and cancer preventive as well as anticancer efficacy in preclinical animal models. This review critically examines the potential role of naturally occurring terpenoids, from diverse origins, in the chemoprevention and treatment of liver tumors. Both in vitro and in vivo effects of these agents and related cellular and molecular mechanisms are highlighted. Potential challenges and future directions involved in the advancement of these promising natural compounds in the chemoprevention and therapy of human liver cancer are also discussed.

Corruption of coronary collateral growth in metabolic syndrome: Role of oxidative stress

The myocardium adapts to ischemic insults in a variety of ways.One adaptation is the phenomenon of acute preconditioning,which can greatly ameliorate ischemic damage.However,this effect wanes within a few hours and does not confer chronic protection.A more chronic adaptation is the so-called second window of preconditioning,which enables protection for a few days.The most potent adaptation invoked by the myocardium to minimize the effects of ischemia is the growth of blood vessels in the heart,angiogenesis and arteriogenesis (collateral growth),which prevent the development of ischemia by enabling flow to a jeopardized region of the heart.This brief review examines the mechanisms underlying angiogenesis and arteriogenesis in the heart.The concept of a redox window,which is an optimal redox state for vascular growth,is discussed along with signaling mechanisms invoked by reactive oxygen species that are stimulated during ischemia-reperfusion.Finally,the review discusses of some of the pathologies,especially the metabolic syndrome,that negatively affect collateral growth through the corruption of redox signaling processes.

Histone Deacetylation Modifier Induced One New Resorcylic Acid Lactone 7′(Z)-zeaenol from the Zoanthid-Derived Fungus Cochliobolus lunatus

Chemical epigenetic manipulation was applied to the zoanthid-derived fungus Cochliobolus lunatus(TA26-46)with a histone deacetylation modifier(100μmol L^(−1) nicotinamide),resulting in the isolation of a new 14-membered resorcylic acid lactone named 7′(Z)-zeaenol(1),together with six known analogues(2−7)from the treated broth.The planar structure of 1 was determined by comprehensive NMR spectroscopy and HRESIMS data.The absolute configuration of 1 was elucidated by ECD spectrum,^(13)C NMR shift calculations,and on the basis of biogenetic considerations.Compound 5 exhibited cytotoxic activity against the human tumor cell lines A549,HCT-116,HT-29,Hela,MCF-7,and K562 with the IC_(50) values ranging from 2.54 to 7.44μmolL^(−1).

Cross-talk between NMDA and GABA_A receptors in cultured neurons of the rat inferior colliculus

Neuronal ion channels of different types often do not function independently but will inhibit or potentiate the activity of other types of channels,a process called cross-talk.The N-methyl-D-aspartate receptor (NMDA receptor) and the γ-aminobutyric acid type A receptor (GABAA receptor) are important excitatory and inhibitory receptors in the central nervous system,respectively.Currently,cross-talk between the NMDA receptor and the GABAA receptor,particularly in the central auditory system,is not well understood.In the present study,we investigated functional interactions between the NMDA receptor and the GABAA receptor using whole-cell patch-clamp techniques in cultured neurons from the inferior colliculus,which is an important nucleus in the central auditory system.We found that the currents induced by aspartate at 100 μmol L-1 were suppressed by the pre-perfusion of GABA at 100 μmol L-1,indicating cross-inhibition of NMDA receptors by activation of GABAA receptors.Moreover,we found that the currents induced by GABA at 100 μmol L-1 (IGABA) were not suppressed by the pre-perfusion of 100 μmol L-1 aspartate,but those induced by GABA at 3 μmol L-1 were suppressed,indicating concentration-dependent cross-inhibition of GABAA receptors by activation of NMDA receptors.In addition,inhibition of IGABA by aspartate was not affected by blockade of voltage-dependent Ca2+ channels with CdCl2 in a solution that contained Ca2+,however,CdCl2 effectively attenuated the inhibition of IGABA by aspartate when it was perfused in a solution that contained Ba2+ instead of Ca2+ or a solution that contained Ca2+ and 10 mmol L-1 BAPTA,a membrane-permeable Ca2+ chelator,suggesting that this inhibition is mediated by Ca2+ influx through NMDA receptors,rather than voltage-dependent Ca2+ channels.Finally,KN-62,a potent inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMKII),reduced the inhibition of IGABA by aspartate,indicating the involvement of CaMKII in this cross-inhibition.Our study demonstrates a functional interaction between NMDA and GABAA receptors in the inferior colliculus of rats.The presence of cross-talk between these receptors suggests that the mechanisms underlying information processing in the central auditory system may be more complex than previously believed.

Masks and thermometers:Paramount measures to stop the rapid spread of SARS-CoV-2 in the United States

In the United States,there is currently an exponential growth for the COVID-19 cases.The US president’s coronavirus guidelines for America“30 Days to Slow The Spread”are necessary.To effectively curb the rapid spread of SARS-CoV-2,two more control measures facemasks and thermometers are strongly suggested to be included in the Guidelines.

High prevalence of consanguineous marriage in a hot foci of hemoglobin Constant Spring in Vietnam

To the editor,Sir,the problem of hemoglobin Constant Spring(Hb Constant Spring)is still a big problem in tropical Indochina.The high prevalence can be seen in this area.According to a recent study by Nguyen VH et al.,the very prevalence on Hb Constant Spring can be seen in the minorities in remote villages of Nam Dong in Central Vietnam^([1]).The observed rate is about 26.2%^([1]),which is significant higher than previous reports among other populations in Indochina^([2,3]).

DNA aptamer S11e recognizes fibrosarcoma and acts as a tumor suppressor

Fibrosarcoma is a serious malignant mesenchymal tumor with strong invasiveness,high recurrence,and poor prognosis.Currently,surgical resection is the main treatment for fibrosarcoma.However,due to the lack of specific biomarkers,the inability to accurately diagnose fibrosarcoma can lead to sub-optimal surgical outcomes and decreased survival.Here,we seek to address this translational barrier and we show that DNA aptamer S11e was able to recognize fibrosarcoma cells(HT1080)but not human embryonic lung fibroblast cells with Kd values in the nanomolar range.In addition,we found that S11e discerned tumors in HT1080 xenograft mouse models and tumor tissues from fibrosarcoma patients.Furthermore,we demonstrated that S11e internalized into HT1080 cells independent of the lysosome pathway and located in mitochondria.Moreover,we revealed that S11e promoted the apoptosis of HT1080 cells and inhibited HT1080 cell migration.Finally,we investigated the biologically functional cellular target of S11e using a mass spectrometry approach,and identified that Diablo/SMAC protein is a cellular binding protein of S11e,by interacting to which S11e inhibited HT1080 cell migration and invasion.Taken together,these results provide the evidence that S11e may be useful for early diagnosis,targeted therapy,and prognostication of fibrosarcoma.

大鼠下丘培养神经元上NMDA与GABA_A受体之间的交互作用

在中枢神经系统中,不同类型的神经元的离子通道往往是通过相互作用而非独立地发挥其功能的,例如,激活一种通道能够抑制或增强另一种通道的功能.N-甲基-D-门冬氨酸受体(NMDA受体)和γ-氨基丁酸A型受体(GABAA受体)分别是中枢神经系统中重要的兴奋性和抑制性的受体.目前,在中枢神经系统中,尤其是在中枢听觉系统中,关于这两种受体的交互作用还没有被详尽地研究.下丘是中枢听觉系统中重要的神经核团.本实验中,在培养的下丘神经元细胞上,利用全细胞膜片钳技术研究了NMDA受体和GABAA受体之间的功能性交互作用.结果发现:(1)100μmol/L的GABA可抑制100μmol/LAsp在下丘神经元激活的全细胞电流(IAsp),表明GABAA受体的激活能够抑制NMDA受体的功能;(2)100μmol/L的Asp对高浓度(100μmol/L)GABA在下丘神经元激活的全细胞电流(IGABA)没有影响,但对低浓度(3μmol/L)GABA激活的IGABA有抑制作用,表明NMDA受体的激活对GABAA受体的抑制作用是浓度依赖性的;(3)细胞外液中加入电压依赖的钙通道(VDCCs)的阻断剂CdCl2不影响Asp对IGABA的抑制作用,但当外液中无钙或在电极内液中加入钙的螯合剂BAPTA时,Asp对IGABA的抑制作用消失,说明这种抑制作用是由钙离子介导的,并且是钙离子通过NMDA受体通道内流而非经由VDCCs内流而发挥作用的;(4)Asp对IGABA的抑制作用可被钙-钙调素依赖性的蛋白激酶Ⅱ(CaMKⅡ)的抑制剂KN-62所阻断,说明在NMDA受体和GABAA受体的功能交互作用中,CaMKⅡ起到了重要的作用.本研究表明,在培养的大鼠下丘神经元上的NMDA受体和GABAA受体之间存在着功能性的交互作用,这两种受体通道之间的交互作用暗示了中枢听觉系统中对于信息加工这一过程可能有着更为复杂的机制.

儿童喘息的诊断

婴儿期和儿童期的喘息是儿童保健院的一种常见病。大约25%～30%的儿童在婴儿期会患一次喘息;而3岁时,患喘息的儿童将占到40%;到了6岁,这个比例将会升至60%。