Stage, survival and delays in lung, colorectal, prostate and ovarian cancer: comparison between diagnostic routes

BACKGROUND: Very few studies have reported cancer outcomes of patients referred through different routes, despite the prominence of current UK cancer urgent referral guidance. AIM: This study aimed to compare outcomes of cancer patients referred through the urgent referral guidance with those who were not, with respect to stage at diagnosis, survival, and delays in diagnosis. Design of study: Analysis of hospital records. SETTING: One hospital trust in England. METHOD: The records of 889 patients diagnosed in 2000-2001 with one of four types of cancer were analysed: 409 with lung cancer; 239 with colorectal cancer; 146 with prostate cancer; and 95 with ovarian cancer. Outcome measures were diagnostic stage, survival, referral and secondary care delays. RESULTS: For lung cancer, urgent referrals had more advanced TNM (tumor, node, metastasis) stage than patients diagnosed through other routes (P = 0.035) and poorer survival (P = 0.020). There was no difference in stage or survival for the other cancers. For each cancer, a higher proportion of urgent referrals was seen within 2 weeks. Secondary care delays for lung and colorectal cancer were shorter for inter-specialty referrals. CONCLUSION: For patients with lung cancer, the guidance appears to be prioritising those in the more advanced stages of disease. This was not the case for the other three cancers. Referral delays were shorter for patients urgently referred, as is the intention of the guidance. The avoidance of delays in outpatient diagnostics probably accounts for shorter secondary care delays for inter-specialty referrals.     

Summation of fibre potentials and the e.m.g.-force relationship during the voluntary movement of a forearm

A linear mathematical model of the electromyogram (e.m.g.) has been developed for the biceps muscle. The number of motor units (and therefore muscle fibres) contributing to the resultant e.m.g. at any stage of movement has been found from the force analysis of elbow flexion. The depths of various motor units and the phase difference between the recruitment of any two motor units have been formulated using a spiral spread of recruitment sequence. The attenuation of individual motor-unit action potentials due to varying depths has been taken into consideration, and due regard has been taken of the length-tension diagram of a muscle while performing the force analysis. Attention has been focused on the flexion of the elbow joint, in which a method of finding the individual contribution of the biceps and brachialis muscles has been developed and applied. The results predicted by the model have been verified by experiments. The model can also be extended to the e.m.g. of other fast skeletal muscles. The conditions and limitations for such generalisations have been stated and discussed.     

Apoptotic body engulfment by a human stellate cell line is profibrogenic

Hepatocyte apoptosis and stellate cell activation are both features of chronic liver diseases, but a relationship between these events has not been explored. In macrophages, engulfment of apoptotic bodies induces expression of transforming growth factor-beta (TGF-beta), a profibrogenic cytokine. We examined whether a similar response occurs in stellate cells. Fluorescently labeled hepatocyte apoptotic bodies were added to cultures of primary and immortalized human stellate cells. Stellate cells, but not hepatocytes, readily engulfed apoptotic bodies in a time-dependent manner as assessed by confocal microscopy. The activation of primary and immortalized human stellate cells after incubation with apoptotic bodies, as well as their fibrogenic activity, was indicated by an increase in alpha-smooth muscle actin (primary cells), TGF-beta1, and collagen alpha1(I) mRNA (primary and immortalized cells). The profibrogenic response was dependent upon apoptotic body engulfment, because nocodazole, a microtubule-inhibiting agent, blocked both the engulfment and the increase of TGF-beta1 and collagen alpha1(I) mRNA. As described in primary rodent stellate cells, up-regulation of collagen alpha1(I) mRNA was inhibited by a PI-3K inhibitor (LY294002) and a p38 mitogen-activated protein kinase inhibitor (SB203580) in LX-1 cells. In conclusion, these data support a model in which engulfment of hepatocyte apoptotic bodies by stellate cells leads to a fibrogenic response by eliciting a kinase-signaling pathway.     

Labeling of cells with ferumoxides-protamine sulfate complexes does not inhibit function or differentiation capacity of hematopoietic or mesenchymal stem cells

Two FDA-approved agents, ferumoxides (Feridex), a suspension of superparamagnetic iron oxide (SPIO) nanoparticles and protamine sulfate, a drug used to reverse heparin anticoagulation, can be complexed and used to label cells magnetically ex vivo. Labeling stem cells with ferumoxides-protamine sulfate (FePro) complexes allows for non-invasive monitoring by MRI. However, in order for stem cell trials or therapies to be effective, this labeling technique must not inhibit the ability of cells to differentiate. In this study, we examined the effect of FePro labeling on stem cell differentiation. Viability, phenotypic expression and differential capacity of FePro labeled CD34 + hematopoietic stem cells (HSC) and mesenchymal stem cells (MSC) were compared with unlabeled control cells. Colony-forming unit (CFU) assays showed that the capacity to differentiate was equivalent for labeled and unlabeled HSC. Furthermore, labeling did not alter expression of surface phenotypic markers (CD34, CD31, CXCR4, CD20, CD3 and CD14) on HSC, as measured by flow cytometry. SDF-1-induced HSC migration and HSC differentiation to dendritic cells were also unaffected by FePro labeling. Both FePro-labeled and unlabeled MSC were cultured in chondrogenesis-inducing conditions. Alcian blue staining for proteoglycans revealed similar chondrogenic differentiation for both FePro-labeled and unlabeled cells. Furthermore, collagen X proteins, indicators of cartilage formation, were detected at similar levels in both labeled and unlabeled cell pellets. Prussian blue staining confirmed that cells in labeled pellets contained iron oxide, whereas cells in unlabeled pellets did not. It is concluded that FePro labeling does not alter the function or differentiation capacity of HSC and MSC. These data increase confidence that MRI studies of FePro-labeled HSC or MSC will provide an accurate representation of in vivo trafficking of unlabeled cells.     

Photodynamic therapy induced Fas-mediated apoptosis in human carcinoma cells

Photodynamic therapy (PDT) is a clinical approach that utilizes light-activated drugs for the treatment of a variety of pathologic conditions. Human poorly (CNE2) and moderately differentiated (TW0-1) human nasopharyngeal carcinoma (NPC) cells undergo rapid apoptosis when treated with PDT sensitized with Hypocrellin A (HA) and Hypocrellin B (HB). It has been shown that these compounds have a strong photodynamic effect on tumors and viruses. The initiating events of PDT sensitized HA and HB-induced apoptosis are poorly defined. In the current study, we sought to determine whether Fas/FasL upregulation and involvement of mitochondrial events are an early event in HA and HB-treated PDT induced apoptosis. Loss of mitochondrial transmembrane potential, release of cytochrome c, involvement of caspases-8 and -3 and the status caspase-3 specific substrate PARP, were evaluated in PDT treated tumor cells. Photoactivation of HA and HB enhanced both CD95/CD95L expression and induced CD95-signaling dependent cell death in all tumor cell lines studied. CD95/ CD95L expression appeared within 2 h following light activation and appeared to be a primary event in PDT induced apoptosis. Furthermore, these results indicate that release of mitochondrial cytochrome c into the cytoplasm is a secondary event following the activation of initiator caspase-8 preceding caspase-3 activation, cleavage of PARP and DNA fragmentation. Cytochrome c appeared in the cytosol within 2-3 h post PDT. Cleavage of PARP was observed at 3-4 h following PDT and caspase-3 specific inhibitor DEVD-CHO and broad-spectrum caspases inhibitor z-VAD-fmk blocked caspase-3 activation and PARP cleavage suggesting that caspase-3 plays an important role in HA and HB-induced apoptosis.     

The Essential Oil of Perilla ocimoides: A Rich Source of Rosefuran

The essential oil of a strain of PERILLA OCIMOIDES from Bangladesh, cultivated at Lucknow, after GC-MS investigations afforded rosefuran ( 1) as the major constituent (58%) along with 17 others including beta-caryophyllene, perilla ketone ( 2), perillene, alpha-cedrene, germacrene-D, and isobis-abolene.     

A Log Ratio-Based Analysis of Individual Changes in the Composition of the Oral Microbiota in Different Dietary Phases

Background: Investigating the influence of nutrition on oral health has a long scientific history. Due to recent technical advances like sequencing techniques for the oral microbiota, this topic has gained scientific interest again. A basic challenge is to understand the influence of nutrition on the oral microbiota and on the interaction between the oral bacteria, which is also statistically challenging. Methods: Log-transformed ratios of two bacteria concentrations are introduced as the basic analytic tool. The framework is illustrated by application in an experimental study exposing eleven participants to different nutrition schemes in five consecutive phases. Results: The method could be sufficiently used to analyse the interrelation between the bacteria and to identify some bacterial groups with the same as well as different reactions to additional dietary components. It was found that the strongest changes in bacterial concentrations were achieved by the additional consumption of dairy products. Conclusion: A log ratio-based analysis offers insights into the relation of different bacteria while taking specific features of compositional data into account. The presented methods allow becoming independent of the behaviour of other bacteria, which is a disadvantage of common analysis methods of compositions. The results indicate that modulations of the oral biofilm microbiota due to nutrition change can be attained.     

Impact of Mental Health Treatment on Suicide Attempts

This paper analyzes the impact of mental health treatment on suicide attempts. While prior work demonstrates the effectiveness of mental health treatment at reducing suicide risk, few studies examine nationally representative populations or use broad measures of access to mental health services. A methodological problem can arise in studies of mental health treatment and suicidal behavior because a suicide attempt can result in the use of more mental health services. Using nationally representative survey data combined with national estimates of provider availability, this paper employs a methodological correction to address that potential problem of reverse causation. This paper uses measures of the density of health care providers in an area as statistical instruments for use of mental health treatment in an analysis of the impact of mental health treatment on suicide attempts. This study finds that mental health treatment significantly reduces suicide attempts.

     

Medical Marijuana Laws,Marijuana Use,and Opioid-Related Outcomes among Women in the United States

BackgroundIn the context of the opioid epidemic, a limited but growing body of literature has found state medical marijuana laws (MMLs) to be associated with lower levels of opioid prescribing. However, robust evidence linking state MMLs with individual-level opioid-related outcomes is lacking, particularly among women. This finding is especially true for pregnant and parenting women, who have been disproportionately affected by the opioid crisis.MethodsUsing data drawn from the 2002–2014 National Survey on Drug Use and Heath, the study uses a difference-in-differences estimation strategy to compare opioid-related outcomes (opioid misuse initiation, opioid misuse in the past month and past year, and opioid use disorder) among all women, pregnant women, and parenting women in states with and without MMLs (before and after implementation). The study also investigates the impact of MMLs on marijuana use and marijuana use disorder.ResultsThe findings indicate that MMLs were not associated with opioid misuse, opioid misuse initiation, or opioid use disorder among all women, pregnant women, and parenting women. These laws were, however, positively correlated with marijuana use and marijuana use disorder among all women and women with children. In addition, MMLs were associated with an increase in the frequency of opioid misuse for pregnant women and a decrease in the frequency of opioid misuse for parenting women.ConclusionsThis finding suggests that, although medical marijuana may be viewed by some as a substitute for opioid analgesics, MMLs may not be an effective policy tool to tackle the opioid epidemic among women, especially pregnant and parenting women.