In vivo treatment with recombinant IL-12 protects C57BL/6J mice against secondary alveolar echinococcosis

Using an experimental model of hepatic Echinococcus multilocularis infection in C57BL/6J mice, intraperitoneal administration of 0.8 μg of recombinant IL-12 to mice with an established infection was shown to reduce the parasite burden as soon as two weeks after the end of treatment. At that time, in vitro Echinococcus multilocularis -induced spleen T cell proliferative responses as well as IFN-γ and IL-5 production were higher in IL-12 treated mice than in untreated mice. Administration of 0.8 μg of IL-12 at the time of infection was shown to be without effect on the parasite establishment. However, this treatment greatly inhibited the subsequent metacestode development. Indeed, ten weeks after infection, it induced a complete healing in 37.5% of mice. At that time, the development of metastases was inhibited in 68.75% of IL-12-treated mice. This reduction of parasite burden was mainly associated with a strong proliferation of spleen cells to E. multilocularis antigen and with a high IFN-γ production. Altogether, our results show that IL-12 is of crucial importance in inhibiting the larval growth after the metacestode establishment in the liver and suggest that this cytokine could be of potential value in the treatment of human alveolar echinococcosis .     

The Collateral Damage of Mass Incarceration: Risk of Psychiatric Morbidity Among Nonincarcerated Residents of High-Incarceration Neighborhoods

Objectives. We examined whether residence in neighborhoods with high levels of incarceration is associated with psychiatric morbidity among nonincarcerated community members.Methods. We linked zip code–linked information on neighborhood prison admissions rates to individual-level data on mental health from the Detroit Neighborhood Health Study (2008–2012), a prospective probability sample of predominantly Black individuals.Results. Controlling for individual- and neighborhood-level risk factors, individuals living in neighborhoods with high prison admission rates were more likely to meet criteria for a current (odds ratio [OR] = 2.9; 95% confidence interval [CI] = 1.7, 5.5) and lifetime (OR = 2.5; 95% CI = 1.4, 4.6) major depressive disorder across the 3 waves of follow-up as well as current (OR = 2.1; 95% CI = 1.0, 4.2) and lifetime (OR = 2.3; 95% CI = 1.2, 4.5) generalized anxiety disorder than were individuals living in neighborhoods with low prison admission rates. These relationships between neighborhood-level incarceration and mental health were comparable for individuals with and without a personal history of incarceration.Conclusions. Incarceration may exert collateral damage on the mental health of individuals living in high-incarceration neighborhoods, suggesting that the public mental health impact of mass incarceration extends beyond those who are incarcerated.The United States leads the world in the percentage of its population that serves time in prison or jail.1,2 As of 2012, nearly 7 million men and women are on probation, parole, or under some other form of community supervision, which means that nearly 3% of the American adult population is currently involved in correctional supervision.3 The burden of incarceration in the United States is not equally distributed in the population. Current estimates from the Bureau of Justice Statistics indicate that 1 of every 3 Black men will serve time in prison in their lifetimes.4 In some communities, these figures are even starker. In Washington, DC, for example, more than 95% of Black men have been in prison in their lifetimes.1 Because of the scope of incarceration within particular subgroups, the current state of the US criminal justice system has been described in such terms as mass imprisonment5 and hyperincarceration.6Research on the health consequences of incarceration falls largely into 2 broad categories. The first, which has received the most empirical attention, has focused on individuals directly involved in the criminal justice system. Individual incarceration exposure is associated with adverse mental7–9 and physical10 health outcomes. A second line of inquiry has evaluated the broader health consequences of incarceration—what has been variously called the “long arm” of corrections,11 the collateral consequences of mass incarceration,5 and “spillover” effects related to incarceration.12 For example, female partners of recently released male prisoners experience depression and anxiety symptoms,13,14 and the children of incarcerated parents are at increased risk for behavioral and mental health problems.15,16 The deleterious health effects of incarceration are not merely confined to the family members of incarcerated individuals, however. Nonincarcerated individuals living in the communities from which inmates are drawn also appear to be at heightened risk for a variety of adverse outcomes, including increased crime rates17 and infectious diseases.18Although this research provides important initial insights into some of the negative consequences of incarceration at the community level, it remains largely unknown whether incarceration influences the mental health of community members who reside in neighborhoods with high-incarceration rates. How might incarceration affect community mental health? High levels of incarceration in neighborhoods can alter the social ecology of communities by eroding social capital and disrupting the kinds of social and family networks and relationships that are necessary for sustaining individuals’ mental health as well as the well-being of communities.1,19–22We examined whether high levels of incarceration in neighborhoods affect the mental health of individuals living in these neighborhoods. We treated incarceration as an ecological or contextual effect, rather than as an individual-level risk factor, which has characterized the majority of research on incarceration and mental health.7,23 That is, rather than examining the mental health consequences of incarceration among those who have themselves been incarcerated or among their family members, we examined the mental health of individuals living in communities that have been exposed to elevated levels of incarceration.     

RP-HPLC法测定β-司他夫定的有关物质

目的:建立了β-司他夫定原料有关物质的RP-HPLC测定方法和水解破坏制备系统适用性试验溶液方法。方法:采用Agilent 1100型高效液相色谱仪,使用SUPELCOSIL LC-18-DB(4.6 mm×250 mm,5μm)色谱柱,以0.01 mol·L-1醋酸铵溶液-乙腈(96.5∶3.5)和0.01 mol·L-1醋酸铵溶液-乙腈(75∶25)为流动相,梯度洗脱,检测波长254 nm,柱温25℃。结果:β-司他夫定和4种已知杂质及其他未知杂质均能达到有效分离;经水解破坏产生的α-司他夫定与β-司他夫定的分离度均达2.8;β-司他夫定、胸腺嘧啶、β-胸苷与5-O’-苯甲酰-司他夫定线性范围分别为0.51~26μg·m L-1(r=1.000)、0.13~27μg·m L-1(r=1.000)、0.50~25μg·m L-1(r=1.000)、1.7~6.3μg·m L-1(r=1.000),已知杂质胸腺嘧啶、β-胸苷与5-O’-苯甲酰-司他夫定的平均加样回收率(n=9)分别为102.8%(RSD=1.5%)、100.6%(RSD=0.9%)、101.9%(RSD=2.1%);β-司他夫定与3种已知杂质的最小检出量均在2.5 ng以下;经水解破坏制备的系统适用性溶液的重复性良好;供试品溶液在4℃下的30 h内基本稳定。结论:本方法灵敏、准确、可靠,专属性强,可用于β-司他夫定原料的有关物质测定。     

Medical marijuana laws and adolescent marijuana use in the United States: a systematic review and meta‐analysis

Aims

To conduct a systematic review and meta‐analysis of studies in order to estimate the effect of US medical marijuana laws (MMLs) on past‐month marijuana use prevalence among adolescents.

Methods

A total of 2999 papers from 17 literature sources were screened systematically. Eleven studies, developed from four ongoing large national surveys, were meta‐analyzed. Estimates of MML effects on any past‐month marijuana use prevalence from included studies were obtained from comparisons of pre–post MML changes in MML states to changes in non‐MML states over comparable time‐periods. These estimates were standardized and entered into a meta‐analysis model with fixed‐effects for each study. Heterogeneity among the study estimates by national data survey was tested with an omnibus F‐test. Estimates of effects on additional marijuana outcomes, of MML provisions (e.g. dispensaries) and among demographic subgroups were abstracted and summarized. Key methodological and modeling characteristics were also described. Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines were followed.

Results

None of the 11 studies found significant estimates of pre–post MML changes compared with contemporaneous changes in non‐MML states for marijuana use prevalence among adolescents. The meta‐analysis yielded a non‐significant pooled estimate (standardized mean difference) of ?0.003 (95% confidence interval = ?0.012, +0.007). Four studies compared MML with non‐MML states on pre‐MML differences and all found higher rates of past‐month marijuana use in MML states pre‐MML passage. Additional tests of specific MML provisions, of MML effects on additional marijuana outcomes and among subgroups generally yielded non‐significant results, although limited heterogeneity may warrant further study.

Conclusions

Synthesis of the current evidence does not support the hypothesis that US medical marijuana laws (MMLs) until 2014 have led to increases in adolescent marijuana use prevalence. Limited heterogeneity exists among estimates of effects of MMLs on other patterns of marijuana use, of effects within particular population subgroups and of effects of specific MML provisions.

     

Corticobasal and ataxia syndromes widen the spectrum of C9ORF72 hexanucleotide expansion disease

Recently, a hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72 was reported as the cause of chromosome 9p21‐linked frontotemporal dementia‐amyotrophic lateral sclerosis (FTD‐ALS). We here report the prevalence of the expansion in a hospital‐based cohort and associated clinical features indicating a wider clinical spectrum of C9ORF72 disease than previously described. We studied 280 patients previously screened for mutations in genes involved in early onset autosomal dominant inherited dementia disorders. A repeat‐primed polymerase chain reaction amplification assay was used to identify pathogenic GGGGCC expansions. As a potential modifier, confirmed cases were further investigated for abnormal CAG expansions in ATXN2. A pathogenic GGGGCC expansion was identified in a total of 14 probands. Three of these presented with atypical clinical features and were previously diagnosed with clinical olivopontocerebellar degeneration (OPCD), atypical Parkinsonian syndrome (APS) and a corticobasal syndrome (CBS). Further, the pathogenic expansion was identified in six FTD patients, four patients with FTD‐ALS and one ALS patient. All confirmed cases had normal ATXN2 repeat sizes. Our study widens the clinical spectrum of C9ORF72related disease and confirms the hexanucleotide expansion as a prevalent cause of FTD‐ALS disorders. There was no indication of a modifying effect of the ATXN2 gene.     

Blood lead levels and growth status among African–American and Hispanic children in Dallas,Texas – 1980 and 2002: Dallas Lead Project II

Objective: The purpose of this investigation is to analyze childhood blood lead levels and growth status (ages 2–12) in Dallas, Texas lead smelter communities in the 1980s and 2002, where smelters operated from 1936 to 1990.

Methods and materials: A sample of convenience study design was used in two cohorts (n=360): 1980–1989 (n=191) and 2002 (n=169). Multivariate analysis of variance and covariance and tandem multiple regressions were used to evaluate the association between stature and blood lead level in two time periods.

Results: In 2002 average child blood lead level (1.6 µg/dL±0.2 SE) was significantly (p<0.001) lower compared to the 1980 cohort mean level (23.6 µg/dL±1.3 SE). Average height and weight in 2002 were 4.5 cm and 4.0 kg greater, respectively, than in 1980. Lowered blood lead level was associated with 3.9 cm, 3.5 kg and 1.1 units greater height, weight and body mass index (BMI), respectively. Cohort effect was associated with greater height (0.6 cm), weight (0.5 kg) and BMI (0.1).

Conclusion: This investigation reports on child growth in a community before and after the transition from high to low blood lead levels over several decades. Using child growth as a proxy, health status of Dallas's lead smelter communities increased markedly over the past two decades, primarily because of lower blood lead levels, while the poverty rate was only marginally lower.     

胃泌素对胃癌细胞SGC7901 Reg Ⅰ基因转录因子的效应

目的 探讨胃泌素对胃癌细胞SGC7901 Reg Ⅰ(Reg Ⅰ)基因转录因子的效应.方法 应用巢式PCR技术从胃癌细胞SGC7901基因组DNA扩增Reg Ⅰ基因启动子1414bp片段,将该片段插入pMD19-T载体,序列分析鉴定.应用随机引物法以地高辛分别标记1414bp及其HindⅢ酶切800bp和614bp片段,经灵敏度检测后,作为探针.应用Genomatix MatInspector在线分析软件分析Reg Ⅰ基因启动子1414bp片段的转录因子结合位点.分别以10-7 mol/L和10-8mol/L胃泌素G-17处理胃癌细胞SGC7901 48h,提取核蛋白.应用DNA-蛋白质印迹法(Southern blotting),分别以地高辛标记的1414bp、800bp和614bp片段为探针检测胃泌素对胃癌细胞SGC7901 Reg Ⅰ基因转录因子的效应.结果 1414bp探针可检测到20条蛋白主带.胃泌素孵育后,带型没有变化,但是一些条带的灰度值改变,带9、12、13、14、15和16的灰度值明显降低(P＜0.05);不同浓度胃泌素处理组之间上述6个条带的灰度值差异不明显(P＞0.05).614bp探针可检测到灰度值变化的6条主带中的带9、12和13,胃泌素处理后,此3条主带的灰度值明显降低(P＜0.05).800bp探针可检测到灰度值变化的6条主带中的带9、12和14,胃泌素处理后,仅带14的灰度值明显降低(P＜0.05).614bp和800bp探针均未检出带15和带16.结论 胃癌细胞SGC7901Reg Ⅰ基因表达由多个转录因子协同调控.降低几个转录因子的结合活性可能是胃泌素上调胃癌细胞SGC7901Reg Ⅰ基因表达的途径之一.     

乙型肝炎病毒对肝内TGF-β1/Smads信号通路的作用

 目的：探讨乙型肝炎病毒（HBV）对肝内TGF-β1蛋白表达及Smads信号通路的作用,为制定慢性乙肝肝纤维化临床治疗策略提供理论依据。方法：(1)运用免疫组化PV-6000法检测对照组和慢性乙肝组肝组织中TGF-β1、HBsAg和HBcAg的表达,并采用荧光定量PCR法测定慢性乙肝患者血清HBV DNA含量。(2)应用体外细胞培养技术培养HBV刺激的人肝星状细胞系LX-2细胞,Western blotting方法测定其细胞内TGF-β1、Smad3和Smad7的蛋白表达。结果：(1)慢性乙肝组肝组织内TGF-β1的表达高于对照组（P＜0.01）;肝内TGF-β1表达水平与血清HBV DNA含量呈正相关（P＜0.01）,且HBcAg阳性肝组织水平较高（P＜0.01）。(2)体外细胞学实验中,HBV刺激组LX-2细胞内TGF-β1和Smad3蛋白含量高于对照组和HBV+抗-TGF-β1组（P＜0.01）;Smad7蛋白表达差异无统计学意义（P>0.05）。结论：(1)TGF-β1在慢性乙肝患者肝组织中的表达与血清HBV DNA含量及肝内HBcAg的表达有关。(2)在TGF-β1/Smads信号通路中,HBV致纤维化作用机制以Smad3的正性调控为主,Smad7的作用不明显。     

血清及尿液特定蛋白检测在糖尿病肾病早期诊断中的意义

目的探讨尿微量白蛋白(MA)、尿α1-微球蛋白(α1-MG)、尿β2-微球蛋白(β2-MG)及血清β2-微球蛋白(β2-MG)在糖尿病肾病早期诊断中的意义。方法收集67例2型糖尿病患者和82名正常健康人的血清及尿液,分别利用化学发光法检测血清β2-MG、放射免疫法测定尿β2-MG及散射速率比浊法测定尿MA和尿α1-MG水平。结果与正常对照组相比,糖尿病组4组特定蛋白水平明显升高,结果有显著性差异(P均<0.05);此4组蛋白在正常对照组测得的结果无一例阳性,但在糖尿病组的阳性率分别为32.8%、47.8%、35.8%、34.3%;实验还发现随着病程的延长,糖尿病组4组蛋白的阳性率也相应升高(P<0.05)。结论测定尿液中MA、α1-MG、β2-MG及血清β2-MG水平对糖尿病肾病的早期诊断具有一定意义,能够帮助患者及早发现病情,减少疾病迁延。     

Brief Report: Transplantation of Allogeneic Canine Bone Marrow Stored at -80 C. in Dimethyl Sulfoxide

Prompt initial bone marrow engraftment was observed in 10 lethally irradiated dogs receiving infusions of 9.8 to 30.0 x 10⁹ allogeneic marrow cellsstored at -80 C. in dimethyl sulfoxide. The 3 recipients of bone marrow fromunrelated donors, mismatched by canine histocompatibility testing, subsequently rejected their grafts and died within 16 days with marrow hypoplasia.The 3 dogs with matched unrelated donors and the 4 with matched littermate donors all showed sustained marrow engraftment. Evidence of marrowrepopulation by allogeneic cells was obtained by cytogenetic studies in oneand by change to donor red cell type in 3 instances.

Submitted on December 16, 1968 Accepted on January 28, 1969