The multi-faceted impact of methamphetamine on Alzheimer’s disease: From a triggering role to a possible therapeutic use

Although it has been initially synthesized for therapeutic purposes and currently FDA-approved and prescribed for obesity, attention-deficit/hyperactivity disorder, narcolepsy and depression, methamphetamine became a recreational drug that is nowadays massively manufactured illegally. Because it is a powerful and extremely addictive psychotropic agent, its abuse has turned out to become a major health problem worldwide. Importantly, the numerous effects triggered by this drug induce neurotoxicity in the brain ultimately leading to serious neurological impairments, tissue damage and neuropsychological disturbances that are reminiscent to most of the symptoms observed in Alzheimer’s disease and other pathological manifestations in aging brain. In this context, there is a growing number of compelling evidence linking methamphetamine abuse with a higher probability of developing premature Alzheimer’s disease and consequent neurodegeneration. This review proposes to establish a broad assessment of the effects that this drug can generate at the cellular and molecular levels in connection with the development of the age-related Alzheimer’s disease. Altogether, the objective is to warn against the long-term effects that methamphetamine abuse may convey on young consumers and the increased risk of developing this devastating brain disorder at later stages of their lives, but also to discuss a more recently emerging concept suggesting a possible use of methamphetamine for treating this pathology under proper and strictly controlled conditions.     

“I don’t want to be Henrietta Lacks”: diverse patient perspectives on donating biospecimens for precision medicine research

PurposeTo determine whether patients distinguish between biospecimens and electronic health records (EHRs) when considering research participation to inform research protections.MethodsWe conducted 20 focus groups with individuals who identified as African American, Hispanic, Chinese, South Asian, and non-Hispanic white on the collection of biospecimens and EHR data for research.ResultsOur study found that many participants did not distinguish between biospecimens and EHR data. However, some participants identified specific concerns about biospecimens. These included the need for special care and respect for biospecimens due to enduring connections between the body and identity; the potential for unacceptable future research, specifically the prospect of human cloning; heightened privacy risks; and the potential for unjust corporate profiteering. Among those who distinguished biospecimens from EHR data, many supported separate consent processes and would limit their own participation to EHR data.ConclusionConsidering that the potential misuse of EHR data is as great as, if not greater than, for biospecimens, more research is needed to understand how attitudes differ between biospecimens and EHR data across diverse populations. Such research should explore mechanisms beyond consent that can address diverse values, perspectives, and misconceptions about sources of patient information to build trust in research relationships.     

“I’ve just never gotten around to doing it”: Men’s approaches to managing BRCA-related cancer risks

Objective

To examine men’s approaches to managing BRCA-related cancer risks.

The “muscular hernia sign”: an original ultrasonographic sign to detect lesions of the forearm’s interosseous membrane

The total disruption of the forearm’s interosseous membrane can lead to an Essex-Lopresti syndrome. The diagnosis must be done early for a better prognostic. Incomplete lesions can aggravate and an early diagnosis of incomplete lesions is a challenging problem. Magnetic resonance imaging is the gold standard but remains expensive, and is hard to obtain in an emergency. On the contrary, ultrasonography is cheap, accessible in an emergency, and dynamical tests can be performed easily. Twelve fresh frozen forearms were randomized in four groups. The membrane was divided into three parts (proximal, middle, and distal thirds). Each group was prepared with variable patterns of lesions. Two radiologists performed an ultrasonographic (US) examination of these forearms. They were blinded with respect to the lesional status of the forearms. Each examination consisted of two stages: static and dynamic. During the dynamic examination, the radiologist looked for the “muscular hernia sign”. The results of their examinations were compared with the real lesional status. The static examination was very efficient in the proximal and middle parts of the membrane, and less reliable in the distal third. With the dynamical examination, no mistake occurred at the proximal and middle parts of the forearm, and there was only one at the distal part. The US examination of the interosseous membrane is very efficient to detect incomplete lesions, mostly, if dynamical tests are performed looking for a “muscular hernia sign”.     

“Unfortunately,I don’t have an answer for you”: How resident physicians communicate diagnostic uncertainty to patients during emergency department discharge

ObjectiveTo describe how emergency medicine resident physicians discuss diagnostic uncertainty during a simulated ED discharge discussion.MethodsA secondary content analysis of simulated clinical encounter audiotapes completed by emergency medicine residents across two sites.ResultsWhen discussing lack of diagnosis, residents explained the evaluation revealed no cause for symptoms, noted concerning diagnoses that were excluded, and acknowledged both symptoms and patients’ feelings. Residents used explicit and implicit language to discuss diagnostic uncertainty with similar frequency. Almost half of the residents discussed the ED role as focused on emergent illness to give patients context for their uncertain diagnoses. However, 28% of residents in this study did not discuss diagnostic uncertainty in any form. All residents provided reassurance.ConclusionResidents use a range of approaches to discuss diagnostic uncertainty with patients at the time of a simulated ED discharge, with some residents omitting discussion of uncertainty entirely.Practice implicationsThese findings represent the current state of communication, which needs improvement. These findings do not immediately transfer to clinical practice recommendations, but rather support a need for both further study and development of formal communication training on this topic.     

Type I cytokine profiles of human naïve and memory B lymphocytes: a potential for memory cells to impact polarization

B cells bifurcating along ‘type 1’ or ‘type 2’ pathways under the influence of polarizing cytokines can, in turn, influence the direction of an immune response. Here, we compare the capacity of human B cells residing within naïve and memory compartments to participate in type 1 polarizing responses. B‐cell receptor (BCR) engagement provided the main signal for interleukin (IL)‐12Rβ1 expression in the two subsets: this was potentiated by CD154 together with interferon‐γ (IFN‐γ) but inhibited by IL‐12. IL‐12Rβ2 could be induced on a minority of B cells by the same signals, and also by IFN‐γ alone. WSX‐1, a receptor for IL‐27, was expressed in both subsets with no evidence for its regulation by the signals studied. While neither subset was capable of secreting much IL‐12 p70, memory B cells could produce a small amount of IL‐12 p40 on CD40 ligation. Memory B cells also, exclusively, expressed IL‐23 p19 mRNA on BCR triggering. Importantly, products of appropriately stimulated memory – but not naive – B cells were shown to promote the synthesis of IFN‐γ in uncommitted T‐helper cells. The data indicate an equal capacity for naïve and memory B cells to respond within a type 1 polarizing environment. Although poorly equipped for initiating type 1 responses, B cells – by virtue of the memory subset – reveal a capacity for their maintenance and amplification following T‐dependent signalling.     

Qualitative evaluation of a narrative reflection program to help medical trainees recognize and avoid overuse: “Am I doing what’s right for the patient?”

Objective

The Do No Harm Project is a novel reflective writing program that encourages medical trainees to reflect on and write up clinical narratives about instances of avoidable medical overuse. Our goal is to describe this program and to explore the effect of the program on those participating.

The impact of perceived calling on work outcomes in a nursing context: The role of career commitment and living one’s calling

The current study examined the impact of perceived calling on nurses’ organizational commitment, organizational citizenship behavior, workplace deviant behavior, and turnover intentions. Moreover, the mediating role of career commitment and the moderating role of living a calling are also investigated. This paper posits a mediated moderation model wherein calling and living a calling interact to predict organizational commitment, organizational citizenship behavior, workplace deviant behavior, and turnover intentions with career commitment mediating the effect of the interaction on the three outcome variables. Data were collected from 294 registered nurses who had worked for a minimum of 6 months in the public or private health care system. Correlation and regression analyses were used to test the proposed hypotheses. Living a calling moderated the effect of calling on career commitment, such that these relations were more robust for nurses with a stronger sense of living a calling. Furthermore, career commitment fully mediated the effect of calling on organizational commitment, organizational citizenship behavior, workplace deviant behavior, and turnover intentions. The indirect effects of career commitment were only significant for nurses with high levels of living a calling. These results imply that possessing a sense of calling brings greater career commitment, which evidently leads to stronger organizational commitment and organizational citizenship behaviors, and lower workplace deviant behavior and turnover intentions. More specifically, nurse's sense of calling could lead to voluntary acts of helping colleagues and participation in organizational activities due to features associated with having a sense of calling, including pro-social intention and other-oriented thoughts. Calling might also decrease turnover intentions and deviant behaviors among nurses. Research about the dynamics of calling in nursing and medical professionals is limited. Recognizing the need, the present research has widened the scope of calling research by investigating the relationships between calling and various work-related variables within Asian nursing context.     

“It’s Got to Be on This Page”: Age and Cognitive Style in a Study of Online Health Information Seeking

BackgroundThe extensive availability of online health information offers the public opportunities to become independently informed about their care, but what affects the successful retrieval and understanding of accurate and detailed information? We have limited knowledge about the ways individuals use the Internet and the personal characteristics that affect online health literacy.ObjectiveThis study examined the extent to which age and cognitive style predicted success in searching for online health information, controlling for differences in education, daily Internet use, and general health literacy.MethodsThe Online Health Study (OHS) was conducted at Johns Hopkins School of Public Health and Stanford University School of Medicine from April 2009 to June 2010. The OHS was designed to explore the factors associated with success in obtaining health information across different age groups. A total of 346 men and women aged 35 years and older of diverse racial and ethnic backgrounds participated in the study. Participants were evaluated for success in searching online for answers to health-related tasks/questions on nutrition, cancer, alternative medicine, vaccinations, medical equipment, and genetic testing.ResultsCognitive style, in terms of context sensitivity, was associated with less success in obtaining online health information, with tasks involving visual judgment most affected. In addition, better health literacy was positively associated with overall success in online health seeking, specifically for tasks requiring prior health knowledge. The oldest searchers were disadvantaged even after controlling for education, Internet use, general health literacy, and cognitive style, especially when spatial tasks such as mapping were involved.ConclusionsThe increasing availability of online health information provides opportunities to improve patient education and knowledge, but effective use of these resources depends on online health literacy. Greater support for those who are in the oldest cohorts and for design of interfaces that support users with different cognitive styles may be required in an age of shared medical decision making.     

The impact of 6-month training preparation for an Ironman triathlon on the proportions of na?ve, memory and senescent T cells in resting blood

Athletes appear to be at a greater risk of illness while undertaking arduous training regimens in preparation for endurance events. As infection susceptibility has been linked with increased proportions of differentiated and senescent T cells in the periphery, changes in the proportions of these cell types due to long-term high-volume exercise training could have important implications for athlete infection risk. This study examined the effects of 6-month training preparation for an Ironman triathlon on the proportions of na?ve, memory and senescent T cells in resting blood. Ten club-level triathletes (9 males; 1 female: 43?±?3?years) were sampled at 27 (December), 21 (January), 15 (March), 9 (May) and 3 (June) weeks before an Ironman Triathlon. An additional sample was collected 2-week post-competition (August). Four-colour flow cytometry was used for the phenotypic analysis of CD4+ and CD8+ blood T cells. Proportions of differentiated (KLRG1+/CD57-) CD8+ T cells and "transitional" (CD45RA+/CD45RO+) CD4+ and CD8+ T cells increased with training, as the values in June were elevated 37, 142 and 116%, respectively, from those observed in December. Proportions of senescent (KLRG1+/CD57+) CD4+ or CD8+ T cells did not change during the training phase. Two weeks post-race, proportions of differentiated CD8+ T cells had returned to baseline values, while the proportions of senescent CD4+ T cells increased 192% alongside a 31% reduction in na?ve (CD45RA+/CD45RO-) cells. In conclusion, increases in differentiated and "transitional" T cells due to arduous exercise training could compromise host protection to novel pathogens and increase athlete infection risk, although whether or not the composition of na?ve and differentiated T cells in blood can serve as prognostic biomarkers in athletes remains to be established.     

The closer ‘We’ are,the stronger ‘I’ am: the impact of couple identity on cancer coping self-efficacy

The present study tested the supposition that greater levels of couple identity (or we-ness) increase a woman’s coping self-efficacy in relation to breast cancer, which, in turn, predicts better psychosocial adjustment. Women (N = 112) in committed relationships completed surveys assessing their levels of couple identity, cancer coping self-efficacy, and aspects of their psychosocial adjustment (specifically, depression, anxiety and functional well-being) during one of their outpatient visits to the cancer centre. As predicted, the more women identified with their relationships, the lower their levels of depression and anxiety were and the greater their functional well-being was. This relationship was mediated by coping self-efficacy: greater identification with one’s relationship predicted greater confidence in one’s ability to cope, which, in turn, predicted better adjustment. The role intimate relationships play in women’s adjustment to breast cancer, as well as directions for further research, are discussed.     

Developing a common framework for evaluating the implementation of genomic medicine interventions in clinical care: the IGNITE Network’s Common Measures Working Group

PurposeImplementation research provides a structure for evaluating the clinical integration of genomic medicine interventions. This paper describes the Implementing Genomics in Practice (IGNITE) Network’s efforts to promote (i) a broader understanding of genomic medicine implementation research and (ii) the sharing of knowledge generated in the network.MethodsTo facilitate this goal, the IGNITE Network Common Measures Working Group (CMG) members adopted the Consolidated Framework for Implementation Research (CFIR) to guide its approach to identifying constructs and measures relevant to evaluating genomic medicine as a whole, standardizing data collection across projects, and combining data in a centralized resource for cross-network analyses.ResultsCMG identified 10 high-priority CFIR constructs as important for genomic medicine. Of those, eight did not have standardized measurement instruments. Therefore, we developed four survey tools to address this gap. In addition, we identified seven high-priority constructs related to patients, families, and communities that did not map to CFIR constructs. Both sets of constructs were combined to create a draft genomic medicine implementation model.ConclusionWe developed processes to identify constructs deemed valuable for genomic medicine implementation and codified them in a model. These resources are freely available to facilitate knowledge generation and sharing across the field.     

Return of incidental findings in genomic medicine: measuring what patients value—development of an instrument to measure preferences for information from next-generation testing (IMPRINT)

PurposeLittle is known about the factors that influence patients’ preferences for the return of incidental findings from genome sequencing. This study identified attributes of incidental findings that were important to patients and developed a discrete-choice experiment instrument to quantify patient preferences.MethodsAn initial set of key attributes and attribute levels was developed from a literature review and in consultation with experts. The attributes’ salience and communication were refined using focus group methodology (n = 12) and cognitive interviews (n = 6) with patients who had received conventional genetic testing for familial colorectal cancer or polyposis syndromes. The attributes and levels used in the hypothetical choices presented to participants were identified using validated experimental design techniques.ResultsThe final discrete-choice experiment instrument incorporates the following attributes and levels: lifetime risk of disease (5, 40, 70%); disease treatability (medical, lifestyle, none); disease severity (mild, moderate, severe); carrier status (yes, no); drug response likelihood (high, moderate, none); and test cost ($250, $425, $1,000, $1,900).ConclusionPatient preferences for incidental genomic findings are likely influenced by a complex set of diverse attributes. Quantification of patient preferences can inform patient–provider communication by highlighting the attributes of incidental findings that matter most to patients and warrant further discussion.