罂粟中阿片依赖机制及药物治疗进展

阿片为罂粟中的主要成分 ,阿片依赖性机制可能涉及脑内奖赏中心、多巴胺 (DA)通路、阿片受体及内源性阿片肽及多种神经递质系统。阿片依赖性治疗主要包括脱毒治疗及防复吸治疗 ,防复吸是目前该领域的研究重点 ,探讨阿片类依赖性机制以开发新药是今后的研究方向。     

Bacterial diversity and community structure of the intestinal microbiome of Channel Catfish (Ictalurus punctatus) during ontogenesis

The acquisition of gut microbes does not occur randomly and is highly dependent on host factors, environmental cues, and self-assembly rules exerted by the microbes themselves. The main objective of this project was to characterize how the gut microbiome develops during the early life stages of Channel Catfish and to identify i) which bacteria are the main constituents of the gut microbiome at different ontogenesis stages, and ii) at which time point(s) the gut microbiome stabilizes. High-throughput Illumina Miseq DNA sequencing of the V4 domain of the 16S rRNA gene was used to assess the microbial community composition during the life stages of Channel Catfish along with water and feed samples. Microbiomes from fertilized eggs, sac fry, swim up fry, pre-fingerlings, and fingerlings were all significantly distinct. OTUs analyses showed that the phylum Proteobacteria, Firmicutes, Fusobacteria and Cyanobacteria dominated the Channel Catfish gut microbiome. During the early stages of ontogenesis, the fish microbiome was dynamic and highly diverse, with significant shifts occurring between fertilized eggs to sac fry (6 dph), and from sac fry to swim up fry (15 dph). The gut microbiome stabilized between the pre-fingerlings and fingerlings stage (≤90 dph) with an observed reduction in species richness. Feed had a more significantly contribution to the microbial colonization of the gut than water. We have identified the period in which the gut microbiome changes rapidly from 15 dph until 21 dph before stabilizing after 90 dph.     

Organization of vertebrate annual cycles: implications for control mechanisms

The majority of vertebrates have a life span of greater than one year. Therefore individuals must be able to adapt to the annual cycle of changing conditions by adjusting morphology, physiology and behaviour. Phenotypic flexibility, in which an individual switches from one life history stage to another, is one way to maximize fitness in a changing environment. When environmental variation is low, few life history stages are needed. If environmental variation is large, there are more life history stages. Each life history stage has a characteristic set of sub-stages that can be expressed in various combinations and patterns to determine state at any point in the life of the individual. Thus individuals have a finite number of states that can be expressed over the spectrum of environmental conditions in their life spans. Life history stages have three phases-development, mature capability (when characteristic sub-stages can be expressed) and termination. Expression of a stage is time dependent (probably a minimum of one month), and termination of one stage overlaps development of the next stage. It follows that the more life history stages an individual expresses, the less flexibility it will have in timing those stages. Having fewer life history stages increases flexibility in timing, but less tolerance of variation in environmental conditions. To varying degrees it is possible to overlap mature capability of some life history stages to effectively reduce 'finite stage diversity' and maximize flexibility in timing. Theoretical ways by which this can be done, and the implications for neuroendocrine and endocrine control mechanisms are discussed. Twelve testable hypotheses are posed that relate directly to control mechanisms.     

Addiction,cognitive decline and therapy: seeking ways to escape a vicious cycle

Any type of behavioral change is an effortful process. Thus, the process of behavioral therapy, where clients seek to change maladaptive behavioral patterns, requires high‐level cognitive engagement. It is unfortunate, then, that cognitive impairment is a feature of substance use disorders (SUDs), and especially because the domains that tend to be impaired are the very ones involved in the process of therapeutic behavioral change. In this review, we compare the cognitive profile that is frequently observed with chronic SUD with the skills that are required to initiate and sustain behavioral change during rehabilitation. Furthermore, we look to new therapeutic developments that seek to improve cognitive function. We propose that the use of these cognitive enhancing agents as adjuncts to behavioral therapy should help to overcome some of the cognitive barriers imposed by the disorder itself, and hence reduce the chance of relapse.     

Regime shifts in exploited marine food webs: detecting mechanisms underlying alternative stable states using size-structured community dynamics theory

Many marine ecosystems have undergone ‘regime shifts’, i.e. abrupt reorganizations across trophic levels. Establishing whether these constitute shifts between alternative stable states is of key importance for the prospects of ecosystem recovery and for management. We show how mechanisms underlying alternative stable states caused by predator–prey interactions can be revealed in field data, using analyses guided by theory on size-structured community dynamics. This is done by combining data on individual performance (such as growth and fecundity) with information on population size and prey availability. We use Atlantic cod (Gadus morhua) and their prey in the Baltic Sea as an example to discuss and distinguish two types of mechanisms, ‘cultivation-depensation’ and ‘overcompensation’, that can cause alternative stable states preventing the recovery of overexploited piscivorous fish populations. Importantly, the type of mechanism can be inferred already from changes in the predators'' body growth in different life stages. Our approach can thus be readily applied to monitored stocks of piscivorous fish species, for which this information often can be assembled. Using this tool can help resolve the causes of catastrophic collapses in marine predatory–prey systems and guide fisheries managers on how to successfully restore collapsed piscivorous fish stocks.     

THE NEW PARADIGM OF RECOVERY FROM SCHIZOPHRENIA: CULTURAL CONUNDRUMS OF IMPROVEMENT WITHOUT CURE

This article is a qualitative investigation of the subjective experience of recovery from the perspective of persons living with schizophrenia-related disorders. An NIMH-sponsored ethnographic study of community outpatient clinics was completed for 90 persons taking second-generation antipsychotic medications. Research diagnostic criteria and clinical ratings were obtained in tandem with an anthropologically developed Subjective Experience of Medication Interview (SEMI) that elicits narrative data on everyday life and activities, medication and treatment, management of symptoms, expectations concerning recovery, and stigma. Ethnographic observations from diverse settings (clinics, public transportation, restaurants, homes) were also obtained. The primary findings are that recovery was experienced in relation to low levels of symptoms, the need to take medications to avoid hospitalization or psychotic episodes, and personal agency to struggle against the effects of illness. The majority of participants articulated their sense of illness recovery and expectation that their lives would improve. Improvement and recovery is an incremental, yet definitively discernable subjective process. Several problems were identified as part of this process surrounding cultural conflicts that generate the experience of ambivalence analyzed here as the “paradox of recovery without cure,” irreconcilable “catch-22” dilemmas involving sacrifice (e.g., one must be “fat” or be “crazy”), and substantial stigma despite improvement in illness and everyday life experience.     

Assessment of forest recovery at Wu-Ling fire scars in Taiwan using multi-temporal Landsat imagery

Normalized Burn Ratio (NBR), a satellite-derived index widely used to map the burned area and to assess burn severity level, was reconceptualized to propose the indices of post-fire recovery condition and resilience. Time series Landsat imagery during 1994–2015 were used to observe the forest recovery of Wu-Ling fire scars in Taiwan. Burn Recovery Ratio (BRR) was newly developed as the indicator to better clarify the forest recovery status. Results show that BRR coupled with dNBR (bi-temporal NBR) could quantitatively describe the level of forest recovery through the heterogeneity of forest landscape which is confirmed by field investigation. Time of complete recovery (t_c), indicator of post-fire resilience, were predicted using curve-fitting of forest recovery trajectories to the exponential decay function. The spatial distribution of t_c could reveal the patterns of post-fire recovery across the fire scars. For wildfire prevention, the issue of fire recurrence should be concerned at the areas of fire-adapted species with low t_c value. For areas of deterioration sites with high t_c value, the rehabilitation project should be implemented to accelerate forest restoration.     

Improving outcomes of first‐episode psychosis: an overview

Outcomes of psychotic disorders are associated with high personal, familiar, societal and clinical burden. There is thus an urgent clinical and societal need for improving those outcomes. Recent advances in research knowledge have opened new opportunities for ameliorating outcomes of psychosis during its early clinical stages. This paper critically reviews these opportunities, summarizing the state‐of‐the‐art knowledge and focusing on recent discoveries and future avenues for first episode research and clinical interventions. Candidate targets for primary universal prevention of psychosis at the population level are discussed. Potentials offered by primary selective prevention in asymptomatic subgroups (stage 0) are presented. Achievements of primary selected prevention in individuals at clinical high risk for psychosis (stage 1) are summarized, along with challenges and limitations of its implementation in clinical practice. Early intervention and secondary prevention strategies at the time of a first episode of psychosis (stage 2) are critically discussed, with a particular focus on minimizing the duration of untreated psychosis, improving treatment response, increasing patients’ satisfaction with treatment, reducing illicit substance abuse and preventing relapses. Early intervention and tertiary prevention strategies at the time of an incomplete recovery (stage 3) are further discussed, in particular with respect to addressing treatment resistance, improving well‐being and social skills with reduction of burden on the family, treatment of comorbid substance use, and prevention of multiple relapses and disease progression. In conclusion, to improve outcomes of a complex, heterogeneous syndrome such as psychosis, it is necessary to globally adopt complex models integrating a clinical staging framework and coordinated specialty care programmes that offer pre‐emptive interventions to high‐risk groups identified across the early stages of the disorder. Only a systematic implementation of these models of care in the national health care systems will render these strategies accessible to the 23 million people worldwide suffering from the most severe psychiatric disorders.     

Effectiveness of information campaigns

Skin cancer represents the most common type of cancer in the white population worldwide and the incidence has dramatically increased during the last decades. UV-radiation is believed to be the most important risk factor responsible for this trend. The prominent role of UV-radiation renders skin cancer most suitable for primary prevention, because the main risk factor can easily be avoided by sticking to simple rules for the behaviour in the sun or under artificial UV (e.g. sunbeds). Since UV-exposure cannot and should not be avoided totally especially due to the beneficial health effects of UV-irradiation like Vitamin D(3)-production, recommendations and information for the public should be as clear and as weighted as possible, through adequate messages, such as: "Love the sun and protect your skin". For that purpose the Association of Dermatological Prevention in Germany (ADP) developed the period of life programme (POLP) that defines certain age-specific target groups, with the aim to give well adapted prevention messages to the population during lifetime. Evaluation of primary prevention campaigns in Germany showed that due to continuous intervention programs during the last 16 years changes in the "sun-behaviour" of the population have been achieved leading to a reduced but sufficient exposure to solar UV-irradiation. This will then contribute to the aim of decreasing morbidity and mortality of skin cancer.     

The weakest link: sensitivity to climate extremes across life stages of marine invertebrates

Predicting the effects of climate change on Earth's biota becomes even more challenging when acknowledging that most species have life cycles consisting of multiple stages, each of which may respond differently to extreme environmental conditions. There is currently no clear consensus regarding which stages are most susceptible to increasing environmental stress, or ‘climate extremes’. We used a meta‐analytic approach to quantify variation in responses to environmental stress across multiple life stages of marine invertebrates. We identified 287 experiments in 29 papers which examined the lethal thresholds of multiple life stages (embryo, larva, juvenile and adult) of both holoplanktonic and meroplanktonic marine invertebrates subjected to the same experimental conditions of warming, acidification and hypoxia stress. Most studies considered short acute exposure to stressors. We calculated effect sizes (log response ratio) for each life stage (unpaired analysis) and the difference in effect sizes between stages of each species (paired analysis) included in each experiment. In the unpaired analysis, all significant responses were negative, indicating that warming, acidification and hypoxia tended to increase mortality. Furthermore, embryos, larvae and juveniles were more negatively affected by warming than adults. The paired analysis revealed that, when subjected to the same experimental conditions, younger life stages were more negatively affected by warming than older life stages, specifically among pairings of adults versus juveniles and larvae versus embryos. Although responses to warming are well documented, few studies of the effects of acidification and hypoxia met the criteria for inclusion in our analyses. Our results suggest that while most life stages will be negatively affected by climate change, younger stages of marine invertebrates are more sensitive to extreme heating events.     

Have we been underestimating the effects of ocean acidification in zooplankton?

Understanding how copepods may respond to ocean acidification (OA) is critical for risk assessments of ocean ecology and biogeochemistry. The perception that copepods are insensitive to OA is largely based on experiments with adult females. Their apparent resilience to increased carbon dioxide (pCO₂) concentrations has supported the view that copepods are ‘winners’ under OA. Here, we show that this conclusion is not robust, that sensitivity across different life stages is significantly misrepresented by studies solely using adult females. Stage‐specific responses to pCO₂ (385–6000 μatm) were studied across different life stages of a calanoid copepod, monitoring for lethal and sublethal responses. Mortality rates varied significantly across the different life stages, with nauplii showing the highest lethal effects; nauplii mortality rates increased threefold when pCO₂ concentrations reached 1000 μatm (year 2100 scenario) with LC₅₀ at 1084 μatm pCO₂. In comparison, eggs, early copepodite stages, and adult males and females were not affected lethally until pCO₂ concentrations ≥3000 μatm. Adverse effects on reproduction were found, with >35% decline in nauplii recruitment at 1000 μatm pCO₂. This suppression of reproductive scope, coupled with the decreased survival of early stage progeny at this pCO₂ concentration, has clear potential to damage population growth dynamics in this species. The disparity in responses seen across the different developmental stages emphasizes the need for a holistic life‐cycle approach to make species‐level projections to climate change. Significant misrepresentation and error propagation can develop from studies which attempt to project outcomes to future OA conditions solely based on single life history stage exposures.     

细胞休眠在肿瘤耐药和复发中的作用

目前对于肿瘤的药物治疗已经取得了一定的进展,然而,治疗后残存肿瘤细胞的复发仍然是导致肿瘤治疗失败的主要原因．肿瘤细胞休眠在肿瘤复发及耐药中发挥着重要的作用．近年来,研究发现上皮间质转化(epithelial-mesenchymal transition,EMT)的肿瘤细胞,肿瘤干细胞(cancer stem cells,CSCs)以及循环肿瘤细胞(circulating tumor cells,CTCs)都显示出细胞周期阻滞的状态．因此,对于休眠阶段肿瘤细胞的研究将可能促进肿瘤的治疗及预防肿瘤的复发．本文总结了药物治疗诱导肿瘤细胞发生休眠的具体过程,同时认为休眠是肿瘤细胞面对药物治疗所采取的主动防御措施,而非被动逃避过程．探究药物诱导性肿瘤细胞的休眠机制对于靶向休眠肿瘤细胞治疗及提高临床治疗效果都具有非常重要的意义．     

Variation in relapse frequency and the transmission potential of Plasmodium vivax malaria

There is substantial variation in the relapse frequency of Plasmodium vivax malaria, with fast-relapsing strains in tropical areas, and slow-relapsing strains in temperate areas with seasonal transmission. We hypothesize that much of the phenotypic diversity in P. vivax relapses arises from selection of relapse frequency to optimize transmission potential in a given environment, in a process similar to the virulence trade-off hypothesis. We develop mathematical models of P. vivax transmission and calculate the basic reproduction number R₀ to investigate how transmission potential varies with relapse frequency and seasonality. In tropical zones with year-round transmission, transmission potential is optimized at intermediate relapse frequencies of two to three months: slower-relapsing strains increase the opportunity for onward transmission to mosquitoes, but also increase the risk of being outcompeted by faster-relapsing strains. Seasonality is an important driver of relapse frequency for temperate strains, with the time to first relapse predicted to be six to nine months, coinciding with the duration between seasonal transmission peaks. We predict that there is a threshold degree of seasonality, below which fast-relapsing tropical strains are selected for, and above which slow-relapsing temperate strains dominate, providing an explanation for the observed global distribution of relapse phenotypes.     

Maternal warming affects early life stages of an invasive thistle

Maternal environment can influence plant offspring performance. Understanding maternal environmental effects will help to bridge a key gap in the knowledge of plant life cycles, and provide important insights for species’ responses under climate change. Here we show that maternal warming significantly affected the early life stages of an invasive thistle, Carduus nutans. Seeds produced by plants grown in warmed conditions had higher germination percentages and shorter mean germination times than those produced by plants under ambient conditions; this difference was most evident at suboptimal germination temperatures. Subsequent seedling emergence was also faster with maternal warming, with no cost to seedling emergence percentage and seedling growth. Our results suggest that maternal warming may accelerate the life cycle of this species via enhanced early life‐history stages. These maternal effects on offspring performance, together with the positive responses of the maternal generation, may exacerbate invasions of this species under climate change.     

The salinity tolerance of freshwater macroinvertebrate eggs and hatchlings in comparison to their older life-stages: a diversity of responses

The tolerance to high salinity of older life stage macroinvertebrates could underestimate the effects of increasing salinity on freshwater macroinvertebrates. The salinity tolerance of the eggs and/or hatchlings of Glyptophysa gibbosa (Planorbidae), Glyptophysa aliciae, Glacidorbis sp. (Glacidorbidae), a Glossiponiidae, Piona cumberlandis (Pionidae), and Chironomus sp. (Chironomidae) were determined. The salinity tolerances of younger life-stages of species studied here and elsewhere were then compared to salinity tolerances of their mature aquatic or dominant life-stage. A diversity of responses have been observed with some species having similar salinity tolerances in all life-stages examined, whilst the eggs or hatchlings of other species had salinity tolerances ranging from 4% to 88% of their older life stages. On present knowledge, this diversity of responses presents some difficulties for simple rules of thumb to approximate sensitivity of young life-stages of freshwater macroinvertebrates inferred from their dominant stage’s tolerance.     

Diet and cancer prevention: Dietary compounds,dietary MicroRNAs,and dietary exosomes

Cancer is one of main health public problems worldwide. Several factors are involved in beginning and development of cancer. Genetic and internal/external environmental factors can be as important agents that effect on emerging and development of several cancers. Diet and nutrition may be as one of important factors in prevention or treatment of various cancers. A large number studies indicated that suitable dietary patterns may help to cancer prevention or could inhibit development of tumor in cancer patients. Moreover, a large numbers studies indicated that a variety of dietary compounds such as curcumin, green tea, folat, selenium, and soy isoflavones show a wide range anti‐cancer properties. It has been showed that these compounds via targeting a sequence of cellular and molecular pathways could be used as suitable options for cancer chemoprevention and cancer therapy. Recently, dietary microRNAs and exosomes have been emerged as attractive players in cancer prevention and cancer therapy. These molecules could change behavior of cancer cells via targeting various cellular and molecular pathways involved in cancer pathogenesis. Hence, the utilization of dietary compounds which are associated with powerful molecules such as microRNAs and exosomes and put them in dietary patterns could contribute to prevention or treatment of various cancers. Here, we summarized various studies that assessed effect of dietary patterns on cancer prevention shortly. Moreover, we highlighted the utilization of dietary compounds, dietary microRNAs, and dietary exosomes and their cellular and molecular pathways in cancer chemoprevention.     

Beliefs About Weight Gain and Attitudes Toward Relapse in a Sample of Women and Men with Obesity

Objective : The purpose of this study was to examine beliefs regarding reasons for weight gain, likely responses to weight loss relapse, notions of reasonable weight loss, and correlations between beliefs and attitudes in a large nonclinical sample of men and women with obesity. Research Methods and Procedures : Participants were 3,394 white women (n= 1,674) and men (n = 1,720) with obesity who had responded to a survey about body image and eating behaviors conducted by Consumer Reports magazine. Results : Women and men indicated that the most important reasons for their weight gain were lack of exercise and enjoying eating; the least important reason was a need to avoid social or sexual situations. Both groups reported that their most likely response to relapse is to start watching food intake, whereas their least likely response is to ask a friend, spouse, or family member for help. Women rated depression, stress, low self-esteem, and need to avoid situations as more important reasons for their weight gain than did men, and women were more likely to feel terrible and regain as a response to relapse. There was no relationship between an individual's beliefs about weight gain, responses to relapse, or notions of reasonable weight loss. Discussion : Implications of these findings for the treatment of obesity are discussed.