Self-Care Behaviors of Ovarian Cancer Patients Before Their Diagnosis: Proof-of-Concept Study

Background: Longer patient intervals can lead to more late-stage cancer diagnoses and higher mortality rates. Individuals may delay presenting to primary care with red flag symptoms and instead turn to the internet to seek information, purchase over-the-counter medication, and change their diet or exercise habits. With advancements in machine learning, there is the potential to explore this complex relationship between a patient’s symptom appraisal and their first consultation at primary care through linkage of existing datasets (eg, health, commercial, and online). Objective: Here, we aimed to explore feasibility and acceptability of symptom appraisal using commercial- and health-data linkages for cancer symptom surveillance. Methods: A proof-of-concept study was developed to assess the general public’s acceptability of commercial- and health-data linkages for cancer symptom surveillance using a qualitative focus group study. We also investigated self-care behaviors of ovarian cancer patients using high-street retailer data, pre- and postdiagnosis. Results: Using a high-street retailer’s data, 1118 purchases—from April 2013 to July 2017—by 11 ovarian cancer patients and one healthy individual were analyzed. There was a unique presence of purchases for pain and indigestion medication prior to cancer diagnosis, which could signal disease in a larger sample. Qualitative findings suggest that the public are willing to consent to commercial- and health-data linkages as long as their data are safeguarded and users of this data are transparent about their purposes. Conclusions: Cancer symptom surveillance using commercial data is feasible and was found to be acceptable. To test efficacy of cancer surveillance using commercial data, larger studies are needed with links to individual electronic health record

Transparent and accurate reporting increases reliability, utility, and impact of your research: reporting guidelines and the EQUATOR Network

Although current electronic methods of scientific publishing offer increased opportunities for publishing all research studies and describing them in sufficient detail, health research literature still suffers from many shortcomings. These shortcomings seriously undermine the value and utility of the literature and waste scarce resources invested in the research. In recent years there have been several positive steps aimed at improving this situation, such as a strengthening of journals' policies on research publication and the wide requirement to register clinical trials

Maternal outcomes comparing normal (referent) group to borderline and GDM groups.

a<p>Adjusted for age, BMI at OGTT, height at OGTT, indoor partner's smoking status, family history of diabetes, family history of hypertension, gestational age at OGTT, baby's sex, parity (not included in model for primary caesarean section), hospitalisation prior to delivery (not included in model for preeclampsia), mean arterial blood pressure at the first antenatal care visit (not included in model for preeclampsia).</p>b<p>For women giving birth vaginally.</p

Outcomes related to the 75-g oral glucose tolerance test results analysed as continuous variables.

a<p>Odds ratios were for an increase in the glucose level of one SD (0.42 mmol/l [7.6 mg/dl] for the fasting plasma glucose level, 1.6 mmol/l [28.9 mg/dl] for the 1-hr plasma glucose level, and 1.4 mmol/l [24.8 mg/dl] for the 2-hr plasma glucose level).</p

Maternal glycaemia and prevalence of gestational diabetes.

a<p>Borderline group is women positive for GDM using the IADPSG criterion, but negative on the ADA criterion.</p

Neonatal outcomes comparing referent group to borderline and GDM groups.

a<p>Adjusted for age, BMI at OGTT, height at OGTT, indoor partner's smoking status, family history of diabetes, family history of hypertension, gestational age at OGTT, baby's sex, parity, hospitalisation prior to delivery, and mean arterial blood pressure at the first antenatal care visit.</p>b<p>Mean (SD), mean difference with 95% confidence intervals.</p>c<p>>90th population percentile for gestational age.</p>d<p><10th population percentile for gestational age.</p>e<p>Intensive neonatal care defined as admission to the neonatal unit for care more intensive than normal newborn care and lasting more than 24 h, excluding suspected sepsis, observation, and feeding problems.</p><p>NA, not applicable.</p

Role of the AP-5 adaptor protein complex in late endosome-to-Golgi retrieval

The AP-5 adaptor protein complex is presumed to function in membrane traffic, but so far nothing is known about its pathway or its cargo. We have used CRISPR-Cas9 to knock out the AP-5 ζ subunit gene, AP5Z1, in HeLa cells, and then analysed the phenotype by subcellular fractionation profiling and quantitative mass spectrometry. The retromer complex had an altered steady-state distribution in the knockout cells, and several Golgi proteins, including GOLIM4 and GOLM1, were depleted from vesicle-enriched fractions. Immunolocalisation showed that loss of AP-5 led to impaired retrieval of the cation-independent mannose 6-phosphate receptor (CIMPR), GOLIM4, and GOLM1 from endosomes back to the Golgi region. Knocking down the retromer complex exacerbated this phenotype. Both the CIMPR and sortilin interacted with the AP-5–associated protein SPG15 in pull-down assays, and we propose that sortilin may act as a link between Golgi proteins and the AP-5/SPG11/SPG15 complex. Together, our findings suggest that AP-5 functions in a novel sorting step out of late endosomes, acting as a backup pathway for retromer. This provides a mechanistic explanation for why mutations in AP-5/SPG11/SPG15 cause cells to accumulate aberrant endolysosomes, and highlights the role of endosome/lysosome dysfunction in the pathology of hereditary spastic paraplegia and other neurodegenerative disorders.The Wellcome Trust https://wellcome.ac.uk/ (grant number 086598). Received by MSR. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. German Research Foundation http://www.dfg.de/ (grant number DFG/Gottfried Wilhelm Leibniz Prize MA 1764/2-1). Contributed to GHHB's research. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The Wellcome Trust https://wellcome.ac.uk/ (grant number 100140). Strategic Award to the CIMR. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Changes in Dopamine Signalling Do Not Underlie Aberrant Hippocampal Plasticity in a Mouse Model of Huntington’s Disease

Altered dopamine receptor labelling has been demonstrated in presymptomatic and symptomatic Huntington's disease (HD) gene carriers, indicating that alterations in dopaminergic signalling are an early event in HD. We have previously described early alterations in synaptic transmission and plasticity in both the cortex and hippocampus of the R6/1 mouse model of Huntington's disease. Deficits in cortical synaptic plasticity were associated with altered dopaminergic signalling and could be reversed by D1- or D2-like dopamine receptor activation. In light of these findings we here investigated whether defects in dopamine signalling could also contribute to the marked alteration in hippocampal synaptic function. To this end we performed dopamine receptor labelling and pharmacology in the R6/1 hippocampus and report a marked, age-dependent elevation of hippocampal D1 and D2 receptor labelling in R6/1 hippocampal subfields. Yet, pharmacological inhibition or activation of D1- or D2-like receptors did not modify the aberrant synaptic plasticity observed in R6/1 mice. These findings demonstrate that global perturbations to dopamine receptor expression do occur in HD transgenic mice, similarly in HD gene carriers and patients. However, the direction of change and the lack of effect of dopaminergic pharmacological agents on synaptic function demonstrate that the perturbations are heterogeneous and region-specific, a finding that may explain the mixed results of dopamine therapy in HD