White matter hyperintensities in vascular contributions to cognitive impairment and dementia (VCID): Knowledge gaps and opportunities

White matter hyperintensities (WMHs) are frequently seen on brain magnetic resonance imaging scans of older people. Usually interpreted clinically as a surrogate for cerebral small vessel disease, WMHs are associated with increased likelihood of cognitive impairment and dementia (including Alzheimer's disease [AD]). WMHs are also seen in cognitively healthy people. In this collaboration of academic, clinical, and pharmaceutical industry perspectives, we identify outstanding questions about WMHs and their relation to cognition, dementia, and AD. What molecular and cellular changes underlie WMHs? What are the neuropathological correlates of WMHs? To what extent are demyelination and inflammation present? Is it helpful to subdivide into periventricular and subcortical WMHs? What do WMHs signify in people diagnosed with AD? What are the risk factors for developing WMHs? What preventive and therapeutic strategies target WMHs? Answering these questions will improve prevention and treatment of WMHs and dementia

What constitutes responsiveness of physicians: A qualitative study in rural Bangladesh

Responsiveness entails the social actions by health providers to meet the legitimate expectations of patients. It plays a critical role in ensuring continuity and effectiveness of care within people centered health systems. Given the lack of contextualized research on responsiveness, we qualitatively explored the perceptions of outpatient users and providers regarding what constitute responsiveness in rural Bangladesh. An exploratory study was undertaken in Chuadanga, a southwestern Bangladeshi District, involving in-depth interviews of physicians (n = 17) and users (n = 7), focus group discussions with users (n = 4), and observations of patient provider interactions (three weeks). Analysis was guided by a conceptual framework of responsiveness, which includes friendliness, respecting, informing and guiding, gaining trust and optimizing benefits. In terms of friendliness, patients expected physicians to greet them before starting consultations; even though physicians considered this unusual. Patients also expected physicians to hold social talks during consultations, which was uncommon. With regards to respect patients expected physicians to refrain from disrespecting them in various ways; but also by showing respect explicitly. Patients also had expectations related to informing and guiding: they desired explanation on at least the diagnosis, seriousness of illness, treatment and preventive steps. In gaining trust, patients expected that physicians would refrain from illegal or unethical activities related to patients, e.g., demanding money against free services, bringing patients in own private clinics by brokers (dalals), colluding with diagnostic centers, accepting gifts from pharmaceutical representatives. In terms of optimizing benefits: patients expected that physicians should be financially sensitive and consider individual need of patients. There were multiple dimensions of responsiveness- for some, stakeholders had a consensus; context was an important factor to understand them. This being an exploratory study, further research is recommended to validate the nuances of the findings. It can be a guideline for responsiveness practices, and a tipping point for future research

PKA Mediates Constitutive Activation of CFTR in Human Sweat Duct

The cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channels are constitutively activated in sweat ducts. Since phosphorylation-dependent and -independent mechanisms can activate CFTR, we sought to determine the actual mechanism responsible for constitutive activation of these channels in vivo. We show that the constitutively activated CFTR Cl− conductance (gCFTR) in the apical membrane is completely deactivated following α-toxin permeabilization of the basolateral membrane. We investigated whether such inhibition of gCFTR following permeabilization is due to the loss of cytoplasmic glutamate or due to dephosphorylation of CFTR by an endogenous phosphatase in the absence of kinase activity (due to the loss of kinase agonist cAMP, cGMP or GTP through α-toxin pores). In order to distinguish between these two possibilities, we examined the effect of inhibiting the endogenous phosphatase activity with okadaic acid (10−8 M) on the permeabilization-induced deactivation of gCFTR. We show that okadaic acid (1) inhibits an endogenous phosphatase responsible for dephosphorylating cAMP but not cGMP or G protein-activated CFTR and (2) prevents deactivation of CFTR following permeabilization of the basolateral membrane. These results indicate that distinctly different phosphatases may be responsible for dephosphorylating different kinase-specific sites on CFTR. We conclude that the phosphorylation by PKA alone appears to be primarily responsible for constitutive activation of gCFTR in vivo

A qualitative study of culturally embedded factors in complementary and alternative medicine use

Abstract Background Within the intercultural milieu of medical pluralism, a nexus of worldviews espousing distinct explanatory models of illness, our research aims at exploring factors leading to complementary and alternative medicine (CAM) use with special attention to their cultural context. Methods The results are based on medical anthropological fieldwork (participant observation and in-depth interviews) spanning a period from January 2015 to May 2017 at four clinics of Traditional Chinese Medicine in Budapest, Hungary. Participant observation involved 105 patients (males N = 42); in-depth interviews were conducted with patients (N = 9) and practitioners (N = 9). The interviews were coded with Interpretative Phenomenological Analysis; all information was aggregated employing Atlas.ti software. Results In order to avoid the dichotomization of “push and pull factors,” results obtained from the fieldwork and interviews were structured along milestones of the patient journey. These points of reference include orientation among sources of information, biomedical diagnosis, patient expectations and the physician-patient relationship, the biomedical treatment trajectory and reasons for non-adherence, philosophical congruence, and alternate routes of entry into the world of CAM. All discussed points which are a departure from the strictly western therapy, entail an underlying socio-cultural disposition and must be scrutinized in this context. Conclusions The influence of one’s culturally determined explanatory model is ubiquitous from the onset of the patient journey and exhibits a reciprocal relationship with subjective experience. Firsthand experience (or that of the Other) signifies the most reliable source of information in matters of illness and choice of therapy. Furthermore, the theme of (building and losing) trust is present throughout the patient journey, a determining factor in patient decision-making and dispositions toward both CAM and biomedicine

MicroRNA-Integrated and Network-Embedded Gene Selection with Diffusion Distance

Gene network information has been used to improve gene selection in microarray-based studies by selecting marker genes based both on their expression and the coordinate expression of genes within their gene network under a given condition. Here we propose a new network-embedded gene selection model. In this model, we first address the limitations of microarray data. Microarray data, although widely used for gene selection, measures only mRNA abundance, which does not always reflect the ultimate gene phenotype, since it does not account for post-transcriptional effects. To overcome this important (critical in certain cases) but ignored-in-almost-all-existing-studies limitation, we design a new strategy to integrate together microarray data with the information of microRNA, the major post-transcriptional regulatory factor. We also handle the challenges led by gene collaboration mechanism. To incorporate the biological facts that genes without direct interactions may work closely due to signal transduction and that two genes may be functionally connected through multi paths, we adopt the concept of diffusion distance. This concept permits us to simulate biological signal propagation and therefore to estimate the collaboration probability for all gene pairs, directly or indirectly-connected, according to multi paths connecting them. We demonstrate, using type 2 diabetes (DM2) as an example, that the proposed strategies can enhance the identification of functional gene partners, which is the key issue in a network-embedded gene selection model. More importantly, we show that our gene selection model outperforms related ones. Genes selected by our model 1) have improved classification capability; 2) agree with biological evidence of DM2-association; and 3) are involved in many well-known DM2-associated pathways

Attitudes towards Human Papillomavirus vaccination among African parents in a city in the north of England: A qualitative study.

Background: Human papillomavirus (HPV) is sexually transmitted and has been conclusively linked to cervical cancer and genital warts. Cervical cancer is attributed to approximately 1100 deaths annually in UK, and is the second most common female cancer globally. It has been suggested that black African women are more predisposed to HPV infection and cervical cancer. A vaccine has been developed to reduce HPV infection, and in the UK, has been offered to 12-13 year old adolescent girls through schools as part of their childhood immunization programme since 2008. Upon programme initiation, it was noted that vaccine uptake was lower in schools where girls from ethnic minority groups were proportionately higher. Objectives: The study’s objectives were to explore factors influencing UK based African parents’ acceptance or decline of the HPV vaccine, whether fathers and mothers share similar views pertaining to vaccination and any interfamily tensions resulting from differing views. Methodology: A qualitative study was conducted with five African couples residing in north England. Face to face semi-structured interviews were carried out. Participants were parents to at least one daughter aged between 8 and 14 years. Recruitment was done through purposive sampling using snowballing. Results: HPV and cervical cancer awareness was generally low, with awareness lower in fathers. HPV vaccination was generally unacceptable among the participants, with fear of promiscuity, infertility and concerns that it’s still a new vaccine with yet unknown side effects cited as reasons for vaccine decline. There was HPV risk denial 3 as religion and good cultural upbringing seemed to result in low risk perceptions, with HPV and cervical cancer generally perceived as a white person’s disease. Religious values and cultural norms influenced vaccine decision-making, with fathers acting as the ultimate decision makers. Current information about why the vaccine is necessary was generally misunderstood. Conclusion: Tailored information addressing religious and cultural concerns may improve vaccine acceptability in African parents

Reversal of aberrant cancer methylome and transcriptome upon direct reprogramming of lung cancer cells

10.1038/srep00592Scientific Reports2

Recognition of depression in people of different cultures: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Many minority group patients who attend primary health care are depressed. To identify a depressive state when GPs see patients from other cultures than their own can be difficult because of cultural and gender differences in expressions and problems of communication. The aim of this study was to explore and analyse how GPs think and deliberate when seeing and treating patients from foreign countries who display potential depressive features.</p> <p>Methods</p> <p>The data were collected in focus groups and through individual interviews with GPs in northern Sweden and analysed by qualitative content analysis.</p> <p>Results</p> <p>In the analysis three themes, based on various categories, emerged; "Realizing the background", "Struggling for clarity" and "Optimizing management". Patients' early life events of importance were often unknown which blurred the accuracy. Reactions to trauma, cultural frictions and conflicts between the new and old gender norms made the diagnostic process difficult. The patient-doctor encounter comprised misconceptions, and social roles in the meetings were sometimes confused. GPs based their judgement mainly on clinical intuition and the established classification of depressive disorders was discussed. Tools for management and adequate action were diffuse.</p> <p>Conclusion</p> <p>Dialogue about patients' illness narratives and social context are crucial. There is a need for tools for multicultural, general practice care in the depressive spectrum. It is also essential to be aware of GPs' own conceptions in order to avoid stereotypes and not to under- or overestimate the occurrence of depressive symptoms</p