Latent factor structure of a behavioral economic cigarette demand curve in adolescent smokers

Behavioral economic demand curves, or quantitative representations of drug consumption across a range of prices, have been used to assess motivation for a variety of drugs. Such curves generate multiple measures of drug demand that are associated with cigarette consumption and nicotine dependence. However, little is known about the relationships among these facets of demand. The aim of the study was to quantify these relationships in adolescent smokers by using exploratory factor analysis to examine the underlying structure of the facets of nicotine incentive value generated from a demand curve measure. Participants were 138 adolescent smokers who completed a hypothetical cigarette purchase task, which assessed estimated cigarette consumption at escalating levels of price/cigarette. Demand curves and five facets of demand were generated from the measure: Elasticity (i.e., 1/α or proportionate price sensitivity); Intensity (i.e., consumption at zero price); O(max) (i.e., maximum financial expenditure on cigarettes); P(max) (i.e., price at which expenditure is maximized); and Breakpoint (i.e., the price that suppresses consumption to zero). Principal components analysis was used to examine the latent structure among the variables. The results revealed a two-factor solution, which were interpreted as "Persistence," reflecting insensitivity to escalating price, and "Amplitude," reflecting the absolute levels of consumption and price. These findings suggest a two factor structure of nicotine incentive value as measured via a demand curve. If supported, these findings have implications for understanding the relationships among individual demand indices in future behavioral economic studies and may further contribute to understanding of the nature of cigarette reinforcement.     

Alpha-2 Adrenergic Receptors and Attention-Deficit/Hyperactivity Disorder

Pharmacologic management of attention-deficit/hyperactivity disorder (ADHD) has expanded beyond stimulant medications to include α-2 adrenergic agonists. These agents exert their actions through presynaptic stimulation and likely involve facilitation of dopamine and noradrenaline neurotransmission, both of which are thought to play critical roles in the pathophysiology of ADHD. Furthermore, frontostriatal dysfunction giving rise to neuropsychological weaknesses has been well-established in patients with ADHD and may explain how α-2 agents exert their beneficial effects. In the following review, we consider relevant neurobiological underpinnings of ADHD with respect to why α-2 agents may be effective in treating this condition. We also review new formulations of α-2 agonists, emerging data on their use in ADHD, and implications for clinical practice. Integrating knowledge of pathophysiologic mechanisms and mechanisms of drug action may inform our medication choices and facilitate treatment of ADHD and related disorders.     

Evidence of Shared Genome‐Wide Additive Genetic Effects on Interpersonal Trauma Exposure and Generalized Vulnerability to Drug Dependence in a Population of Substance Users

Exposure to traumatic experiences is associated with an increased risk for drug dependence and poorer response to substance abuse treatment (Claus & Kindleberger, 2002; Jaycox, Ebener, Damesek, & Becker, 2004). Despite this evidence, the reasons for the observed associations of trauma and the general tendency to be dependent upon drugs of abuse remain unclear. Data (N = 2,596) from the Study of Addiction: Genetics and Environment were used to analyze (a) the degree to which commonly occurring single nucleotide polymorphisms (SNPs; minor allele frequency > 1%) in the human genome explains exposure to interpersonal traumatic experiences, and (b) the extent to which additive genetic effects on trauma are shared with additive genetic effects on drug dependence. Our results suggested moderate additive genetic influences on interpersonal trauma, h²_{SNP‐Interpersonal} = .47, 95% confidence interval (CI) [.10, .85], that are partially shared with additive genetic effects on generalized vulnerability to drug dependence, h²_SNP‐DD = .36, 95% CI [.11, .61]; r_G‐SNP = .49, 95% CI [.02, .96]. Although the design/technique does not exclude the possibility that substance abuse causally increases risk for traumatic experiences (or vice versa), these findings raise the possibility that commonly occurring SNPs influence both the general tendency towards drug dependence and interpersonal trauma.     

Anaerobic infections of the lung

Although the landmark investigational period for anaerobic pathogens occurred more than 20 years ago, pleuropulmonary infections caused by these pathogens remain an important cause of morbidity and mortality. Despite heightened awareness of pathogenicity and new diagnostic methods, the actual incidence of anaerobes in pulmonary infections—especially those occurring in hospitalized patients—remains controversial. Further complicating the management of these infections is the changing antimicrobial susceptibility of oral anaerobes, which has mandated the abandonment of penicillin monotherapy in seriously ill patients. This article reviews the pathogenesis of anaerobic pulmonary infections, their clinical presentations, and current management issues.     

犬内皮与平滑肌细胞的短期静态联合培养

目的:为获得组织工程化自体血管,观察体外静态培养条件下犬内皮细胞与平滑肌细胞联合培养组织学及形态学的特征。方法:实验于2004-07/2005-06在首都医科大学宣武医院外科院级实验室完成。①实验材料:雄性杂种犬,3个月龄,体质量8～12kg。②实验方法:贴块法及酶解法对犬内皮细胞及平滑肌细胞进行原代分离培养及扩增,将第Ⅱ代平滑肌细胞以1×109L-1的密度种植于胶原膜上培养13d,再将第Ⅱ代内皮细胞接种于生长平滑肌细胞的胶原膜上2d。③实验评估:行苏木精-伊红染色同时扫描电镜和透射电镜观察平滑肌细胞和内皮细胞在胶原载体上联合培养后的形态。结果:苏木精-伊红染色见平滑肌细胞较均匀的分布于支架材料表面及内部;扫描电镜下,平滑肌细胞可以在胶原载体材料上生长,增殖明显并在短期内形成多层细胞。内皮细胞与平滑肌细胞联合培养2d就可在平滑肌细胞层表面获得连续的单层内皮细胞层。结论:在短期静态培养条件下犬的血管平滑肌细胞和内皮细胞可以在胶原载体材料上形成具有两层细胞结构的组织工程化动脉血管组织片。     

自体骨髓干细胞移植治疗失代偿期肝硬化

选择36例失代偿期肝硬化患者,年龄37～59岁,患者在无菌条件下,从髂后上棘抽取骨髓100～200mL,在体外分离纯化骨髓干细胞后,局部麻醉下经股动脉插管经肝动脉将分离的骨髓干细胞移植于肝脏。自移植后12周,25例(69.4%)患者谷丙转氨酶逐渐降低,由平均(2788.56±357.90)nkat/L降至(1077.05±440.25)nkat/L;22例(61.1%)患者总胆红素逐渐下降,由平均(151.47±25.77)μmol/L降至(69.93±18.86)μmol/L;27例(75%)患者白蛋白逐渐升高,由平均(25.17±11.79)g/L升至(30.87±12.17)g/L。在干细胞移植后凝血酶原活动度逐渐上升,由术前平均(25.89±12.67)%上升至术后12周的(50.39±19.38)%,患者凝血机制明显改善。移植后大多数患者身体状况有明显的改善;移植后12周腹水减轻的19例(52.7%),食欲改善的28例(77.7%),体力好转20例(58.3%),腹胀减轻17例(47.2%),36例干细胞移植患者未出现严重并发症。     

A humanised tissue‐engineered bone model allows species‐specific breast cancer‐related bone metastasis in vivo

Bone metastases frequently occur in the advanced stages of breast cancer. At this stage, the disease is deemed incurable. To date, the mechanisms of breast cancer‐related metastasis to bone are poorly understood. This may be attributed to the lack of appropriate animal models to investigate the complex cancer cell–bone interactions. In this study, two established tissue‐engineered bone constructs (TEBCs) were applied to a breast cancer‐related metastasis model. A cylindrical medical‐grade polycaprolactone‐tricalcium phosphate scaffold produced by fused deposition modelling (scaffold 1) was compared with a tubular calcium phosphate‐coated polycaprolactone scaffold fabricated by solution electrospinning (scaffold 2) for their potential to generate ectopic humanised bone in NOD/SCID mice. While scaffold 1 was found not suitable to generate a sufficient amount of ectopic bone tissue due to poor ectopic integration, scaffold 2 showed excellent integration into the host tissue, leading to bone formation. To mimic breast cancer cell colonisation to the bone, MDA‐MB‐231, SUM1315, and MDA‐MB‐231BO breast cancer cells were cultured in polyethylene glycol‐based hydrogels and implanted adjacent to the TEBCs. Histological analysis indicated that the breast cancer cells induced an osteoclastic reaction in the TEBCs, demonstrating analogies to breast cancer‐related bone metastasis seen in patients.