Monocyte chemotaxis in bronchial carcinoma and cigarette smokers.

Chemotaxis of blood monocytes was measured in 31 patients with bronchial carcinoma and 19 cigarette smokers. Thirteen patients with metastatic bronchial carcinoma had significantly less (P less than 0.005) chemotactic response than matched controls. Those with disease confined to the chest, or with recurrent or operable bronchial carcinoma, had no significant depression of monocyte chemotaxis. There was also no significant difference in monocyte chemotaxis between cigarette smokers and matched controls. These results support the concept that in human cancer there is a defect in monocyte chemotaxis, but in bronchial carcinoma significant depression was only apparent in those with advanced disease

Deal or no-deal? Using administrative data to explore buyer motivation in online drug purchases and its association with community risk factors in Scotland

Background The expansion of online drugs markets has widened opportunities to purchase drugs, for both personal use and wider distribution, thus creating new potential public health risks. However, there is little research on the motivation of online drug purchasers or the level of risk that such transactions pose to different communities. Greater insights into the intended use of drug parcels arriving by post, and how this varies across communities could help law enforcement and health services develop more effective policies and better allocate resources to reduce drug-related harms. Methods We use Scottish administrative data about illegal drug parcels seized by the UK Border Force to create a new classification of ‘buyer motivation’ (based on type of drug, estimated number of doses purchased, and patterns of drug consumption). We identify three potential types of buyer motivation: personal consumption, heavy use or social dealing, and wholesale dealing; and examine the extent to which each type is associated with a range of drug-related community risk factors, thereby identifying potential variation in levels of public health risk. Results Communities to which drug parcels were destined differed significantly from the Scottish average across a range of factors; however, this varied by buyer motivation. Parcels thought to be purchased for heavy use or social dealing appeared to pose a greater risk within communities characterised by general deprivation, but especially health-related deprivation, with a high youth population but low unemployment rates; whereas those purchased for wholesale dealing appear most likely to pose a risk in communities with higher crime and unemployment rates. Conclusions Administrative data about intercepted drug parcels could be helpful in classifying the motivation of online drug purchasers and monitoring patterns of variation in potential public health risks at a community level. This could support law enforcement and public health agencies to develop more targeted drug-harm reduction strategies

Altered functional brain network connectivity and glutamate system function in transgenic mice expressing truncated Disrupted-in-Schizophrenia 1

Considerable evidence implicates DISC1 as a susceptibility gene for multiple psychiatric diseases. DISC1 has been intensively studied at the molecular, cellular and behavioral level, but its role in regulating brain connectivity and brain network function remains unknown. Here, we utilize a set of complementary approaches to assess the functional brain network abnormalities present in mice expressing a truncated Disc1 gene (Disc1tr Hemi mice). Disc1tr Hemi mice exhibited hypometabolism in the prefrontal cortex (PFC) and reticular thalamus along with a reorganization of functional brain network connectivity that included compromised hippocampal–PFC connectivity. Altered hippocampal–PFC connectivity in Disc1tr Hemi mice was confirmed by electrophysiological analysis, with Disc1tr Hemi mice showing a reduced probability of presynaptic neurotransmitter release in the monosynaptic glutamatergic hippocampal CA1–PFC projection. Glutamate system dysfunction in Disc1tr Hemi mice was further supported by the attenuated cerebral metabolic response to the NMDA receptor (NMDAR) antagonist ketamine and decreased hippocampal expression of NMDAR subunits 2A and 2B in these animals. These data show that the Disc1 truncation in Disc1tr Hemi mice induces a range of translationally relevant endophenotypes underpinned by glutamate system dysfunction and altered brain connectivity

Development and psychometric testing of a breast cancer patient-profiling questionnaire

Introduction: The advent of \u201cpersonalized medicine\u201d has been driven by technological advances in genomics. Concentration at the subcellular level of a patient\u2019s cancer cells has meant inevitably that the \u201cperson\u201d has been overlooked. For this reason, we think there is an urgent need to develop a truly personalized approach focusing on each patient as an individual, assessing his/her unique mental dimensions and tailoring interventions to his/her individual needs and preferences. The aim of this study was to develop and test the psychometric properties of the ALGA-Breast Cancer (ALGA-BC), a new multidimensional questionnaire that assesses the breast cancer patient\u2019s physical and mental characteristics in order to provide physicians, prior to the consultation, with a patient\u2019s profile that is supposed to facilitate subsequent communication, interaction, and information delivery between the doctor and the patient. Methods: The specific validation processes used were: content and face validity, construct validity using factor analysis, reliability and internal consistency using test\u2013retest reliability, and Cronbach\u2019s alpha correlation coefficient. The exploratory analysis included 100 primary breast cancer patients and 730 healthy subjects. Results: The exploratory factor analysis revealed eight key factors: global self-rated health, perceived physical health, anxiety, self-efficacy, cognitive closure, memory, body image, and sexual life. Test\u2013retest reliability and internal consistency were good. Comparing patients with a sample of healthy subjects, we also observed a general ability of the ALGA-BC questionnaire to discriminate between the two. Conclusion: The ALGA-BC questionnaire with 29 items is a valid instrument with which to obtain a patient\u2019s profile that is supposed to help physicians achieve meaningful personalized care which supplements biological and genetic analyse

Phase II study of ACNU in non-small-cell lung cancer: EORTC study 08872

A total of 62 patients with metastatic or locally advanced non-small-cell lung cancer were entered in a phase II study of ACNU. Initially, the drug was given i. v. at a dose of 100 mg/m2 every 6 weeks, but due to observed haematological side effects in chemotherapy-pretreated patients, the dose was lowered in this group to 75 mg/m2. We observed one complete response in a subject exhibiting multiple lung metastases and a partial response in two patients, one showing brain metastases and one who experienced local disease recurrence. The toxicity of ACNU mainly consisted of bone marrow suppression especially thrombocytopenia, with one toxic death occurring due to intracerebral haemorrhage. We concluded that at this dose and on this schedule, ACNU has limited activity in non-small-cell lung cancer

Altered functional brain network connectivity and glutamate system function in transgenic mice expressing truncated Disrupted-in-Schizophrenia 1

Considerable evidence implicates DISC1 as a susceptibility gene for multiple psychiatric diseases. DISC1 has been intensively studied at the molecular, cellular and behavioral level, but its role in regulating brain connectivity and brain network function remains unknown. Here, we utilize a set of complementary approaches to assess the functional brain network abnormalities present in mice expressing a truncated Disc1 gene (Disc1tr Hemi mice). Disc1tr Hemi mice exhibited hypometabolism in the prefrontal cortex (PFC) and reticular thalamus along with a reorganization of functional brain network connectivity that included compromised hippocampal-PFC connectivity. Altered hippocampal-PFC connectivity in Disc1tr Hemi mice was confirmed by electrophysiological analysis, with Disc1tr Hemi mice showing a reduced probability of presynaptic neurotransmitter release in the monosynaptic glutamatergic hippocampal CA1-PFC projection. Glutamate system dysfunction in Disc1tr Hemi mice was further supported by the attenuated cerebral metabolic response to the NMDA receptor (NMDAR) antagonist ketamine and decreased hippocampal expression of NMDAR subunits 2A and 2B in these animals. These data show that the Disc1 truncation in Disc1tr Hemi mice induces a range of translationally relevant endophenotypes underpinned by glutamate system dysfunction and altered brain connectivity