'Willy nilly' doctors, bad patients, and resistant bodies in general public explanations of antimicrobial resistance

Increased public engagement is a feature of policy and communications focussed on the reduction of antimicrobial resistance. Explaining antimicrobial resistance for general publics has proven difficult and they continue to endorse apparently mistaken knowledge, including the conflation of antimicrobial resistance with the notion of the resistant body. We interviewed members of the general public in Melbourne, Australia, to explore explanatory models for antimicrobial resistance and shed light on the persistence of the resistant body assumption and related concepts. In the face of AMR’s complexity and the portended antibiotic apocalypse, publics rely on a heavily inscribed understanding of the body defending itself against microbes. Publics also read antibiotic misuse and overuse messages as the responsibility of other patients and medical practitioners, and not themselves. Significantly, the scientific world view that has created expert knowledge about AMR hails publics in ways that discredits them and limits their capacity to take action. Increased engagement with publics will be required to ensure that collaborative and sustainable AMR approaches are fashioned for the future

SLC6A3 and body mass index in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

<p>Abstract</p> <p>Background</p> <p>To investigate the contribution of the dopamine transporter to dopaminergic reward-related behaviors and anthropometry, we evaluated associations between polymorphisms at the dopamine transporter gene(<it>SLC6A3</it>) and body mass index (BMI), among participants in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.</p> <p>Methods</p> <p>Four polymorphisms (rs6350, rs6413429, rs6347 and the 3' variable number of tandem repeat (3' VNTR) polymorphism) at the <it>SLC6A3 </it>gene were genotyped in 2,364 participants selected from the screening arm of PLCO randomly within strata of sex, age and smoking history. Height and weight at ages 20 and 50 years and baseline were assessed by questionnaire. BMI was calculated and categorized as underweight, normal, overweight and obese (<18.5, 18.5–24.9, 25.0–29.9, or ≥ 30 kg/m², respectively). Odds ratios (ORs) and 95% confidence intervals (CIs) of <it>SLC6A3 </it>genotypes and haplotypes were computed using conditional logistic regression.</p> <p>Results</p> <p>Compared with individuals having a normal BMI, obese individuals at the time of the baseline study questionnaire were less likely to possess the <it>3' </it>VNTR variant allele with 9 copies of the repeated sequence in a dose-dependent model (** is referent; OR_*9= 0.80, OR₉₉= 0.47, p_trend= 0.005). Compared with individuals having a normal BMI at age 50, overweight individuals (A-C-G-* is referent; OR_A-C-G-9= 0.80, 95% CI 0.65–0.99, p = 0.04) and obese individuals (A-C-G-* is referent; OR_A-C-G-9= 0.70, 95% CI 0.49–0.99, p = 0.04) were less likely to possess the haplotype with the 3'variant allele (A-C-G-9).</p> <p>Conclusion</p> <p>Our results support a role of genetic variation at the dopamine transporter gene, <it>SLC6A3</it>, as a modifier of BMI.</p

Genetic counselling and the intention to undergo prophylactic mastectomy: effects of a breast cancer risk assessment

Scientific reports suggest that women at risk for familial breast cancer may benefit from prophylactic mastectomy. However, few data are available about how women decide upon this clinical option, and in particular, what role an objective risk assessment plays in this. The purpose of the present study is to assess whether this objective risk information provided in genetic counselling affects the intention for prophylactic mastectomy. Additionally, the (mediating) effects of breast cancer worry and perceived risk are investigated. A total of 241 women completed a questionnaire before and after receiving information about their familial lifetime breast cancer risk in a genetic counselling session. Path analysis showed that the objective risk information had a corrective effect on perceived risk (β=0.38; P=0.0001), whereas the amount of breast cancer worry was not influenced by the counselling session. The objective risk information did not directly affect the intention for prophylactic mastectomy. The intention was influenced by perceived risk after counselling (β=0.23; P=0.002), and by the precounselling levels of perceived risk (β=0.27; P=0.00025) and breast cancer worry (β=0.32; P=0.0001), that is, higher levels of perceived risk and breast cancer worry imply a stronger intention for prophylactic mastectomy. A personal history of breast cancer did not directly influence the intention for prophylactic mastectomy, but affected women who had undergone a mastectomy as surgical treatment were more positively inclined to have a prophylactic mastectomy than women who had had breast-conserving therapy. The impact of objective risk information on the intention for prophylactic mastectomy is limited and is mediated by perceived risk. Important determinants of the intention for prophylactic mastectomy were precounselling levels of breast cancer worry and perceived risk, suggesting that genetic counselling is only one event in the entire process of decision making. Therefore, interventions aimed at improving decision making on prophylactic mastectomy should explicitly address precounselling factors, such as personal beliefs and the psychological impact of the family medical history

Influences of polymorphic variants of DRD2 and SLC6A3 genes, and their combinations on smoking in Polish population

<p>Abstract</p> <p>Background</p> <p>Polymorphisms in dopaminergic genes may influence cigarette smoking by their potential impact on dopamine reward pathway function. <it>A1 </it>allele of <it>DRD2 </it>gene is associated with a reduced dopamine D2 receptor density, and it has been hypothesised that <it>A1 </it>carriers are more vulnerable to smoking. In turn, the 9-repeat allele of dopamine transporter gene (<it>SLC6A3</it>) has been associated with a substantial reduction in dopamine transporter, what might result in the higher level of dopamine in the synaptic cleft, and thereby protective role of this allele from smoking. In the present study we investigated whether polymorphic variants of <it>DRD2 </it>and <it>SLC6A3 </it>genes and their combinations are associated with the smoking habit in the Polish population.</p> <p>Methods</p> <p>Genotyping for <it>Taq</it>I<it>A </it>polymorphism of <it>DRD2 </it>and <it>SLC6A3 </it>VNTR polymorphism was performed in 150 ever-smokers and 158 never-smokers. The association between the smoking status and smoking phenotypes (related to the number of cigarettes smoked daily and age of starting regular smoking), and genotype/genotype combinations was expressed by ORs together with 95% CI. Alpha level of 0.05, with Bonferroni correction whenever appropriate, was used for statistical significance.</p> <p>Results</p> <p>At the used alpha levels no association between <it>DRD2 </it>and <it>SLC6A</it>3 genotypes and smoking status was found. However, <it>A1 </it>allele carriers reported longer abstinence periods on quitting attempts than non-carriers (p = 0.049). The ORs for heavier smoking were 0.38 (0.17-0.88), p = 0.023, and 0.39 (0.17-0.88), p = 0.021 in carriers compared to non-carriers of <it>A1 </it>or <it>*9 </it>allele, respectively, and the OR for this smoking phenotype was 8.68 (2.47-30.46), p = 0.0005 for the <it>A1</it>-/<it>9</it>- genotype combination, relatively to the <it>A1</it>+/<it>9</it>+. Carriers of <it>*9 </it>allele of <it>SLC6A3 </it>had over twice a lower risk to start smoking before the age of 20 years compared to non-carriers (sex-adjusted OR = 0.44; 95% CI: 0.22-0.89; p = 0.0017), and subjects with <it>A1-/9- </it>genotype combination had a higher risk for staring regular smoking before the age of 20 years in comparison to subjects with <it>A1+/9+ </it>genotype combination (sex-adjusted OR = 3.79; 95% CI:1.03-13.90; p = 0.003).</p> <p>Conclusion</p> <p>Polymorphic variants of <it>DRD2 </it>and <it>SLC6A3 </it>genes may influence some aspects of the smoking behavior, including age of starting regular smoking, the level of cigarette consumption, and periods of abstinence. Further large sample studies are needed to verify this hypothesis.</p

Absence of Colony Stimulation Factor-1 Receptor Results in Loss of Microglia, Disrupted Brain Development and Olfactory Deficits

The brain contains numerous mononuclear phagocytes called microglia. These cells express the transmembrane tyrosine kinase receptor for the macrophage growth factor colony stimulating factor-1 (CSF-1R). Using a CSF-1R-GFP reporter mouse strain combined with lineage defining antibody staining we show in the postnatal mouse brain that CSF-1R is expressed only in microglia and not neurons, astrocytes or glial cells. To study CSF-1R function we used mice homozygous for a null mutation in the Csflr gene. In these mice microglia are >99% depleted at embryonic day 16 and day 1 post-partum brain. At three weeks of age this microglial depletion continues in most regions of the brain although some contain clusters of rounded microglia. Despite the loss of microglia, embryonic brain development appears normal but during the post-natal period the brain architecture becomes perturbed with enlarged ventricles and regionally compressed parenchyma, phenotypes most prominent in the olfactory bulb and cortex. In the cortex there is increased neuronal density, elevated numbers of astrocytes but reduced numbers of oligodendrocytes. Csf1r nulls rarely survive to adulthood and therefore to study the role of CSF-1R in olfaction we used the viable null mutants in the Csf1 (Csf1op) gene that encodes one of the two known CSF-1R ligands. Food-finding experiments indicate that olfactory capacity is significantly impaired in the absence of CSF-1. CSF-1R is therefore required for the development of microglia, for a fully functional olfactory system and the maintenance of normal brain structure

CSF1R mutations in hereditary diffuse leukoencephalopathy with spheroids are loss of function

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) in humans is a rare autosomal dominant disease characterized by giant neuroaxonal swellings (spheroids) within the CNS white matter. Symptoms are variable and can include personality and behavioural changes. Patients with this disease have mutations in the protein kinase domain of the colony-stimulating factor 1 receptor (CSF1R) which is a tyrosine kinase receptor essential for microglia development. We investigated the effects of these mutations on Csf1r signalling using a factor dependent cell line. Corresponding mutant forms of murine Csf1r were expressed on the cell surface at normal levels, and bound CSF1, but were not able to sustain cell proliferation. Since Csf1r signaling requires receptor dimerization initiated by CSF1 binding, the data suggest a mechanism for phenotypic dominance of the mutant allele in HDLS