Cannabis, Cannabinoids, and Stroke: Increased Risk or Potential for Protection-A Narrative Review.

Worldwide, approximately 15 million people per year suffer from stroke. With about 5 million deaths, stroke is the second most common cause of death and a major cause of long-term disability. It is estimated that about 25% of people older than 85 years will develop stroke. Cannabis sativa and derived cannabinoids have been used for recreational and medical purposes for many centuries. However, due to the legal status in the past, research faced restrictions, and cannabis use was stigmatized for potential negative impacts on health. With the changes in legal status in many countries of the world, cannabis and cannabis-derived substances such as cannabinoids and terpenes have gained more interest in medical research. Several medical effects of cannabis have been scientifically proven, and potential risks identified. In the context of stroke, the role of cannabis is controversial. The negative impact of cannabis use on stroke has been reported through case reports and population-based studies. However, potential beneficial effects of specific cannabinoids are described in animal studies under certain conditions. In this narrative review, the existing body of evidence regarding the negative and positive impacts of cannabis use prior to stroke will be critically appraised.

Unilateral Mitochondrial-Hemodynamic Coupling and Bilateral Connectivity in the Prefrontal Cortices of Young and Older Healthy Adults.

A recent study demonstrated that noninvasive measurements of cortical hemodynamics and metabolism in the resting human prefrontal cortex can facilitate quantitative metrics of unilateral mitochondrial-hemodynamic coupling and bilateral connectivity in infraslow oscillation frequencies in young adults. The infraslow oscillation includes three distinct vasomotions with endogenic (E), neurogenic (N), and myogenic (M) frequency bands. The goal of this study was to prove the hypothesis that there are significant differences between young and older adults in the unilateral coupling (uCOP) and bilateral connectivity (bCON) in the prefrontal cortex. Accordingly, we performed measurements from 24 older adults (67.2 ± 5.9 years of age) using the same two-channel broadband near-infrared spectroscopy (bbNIRS) setup and resting-state experimental protocol as those in the recent study. After quantification of uCOP and bCON in three E/N/M frequencies and statistical analysis, we demonstrated that older adults had significantly weaker bilateral hemodynamic connectivity but significantly stronger bilateral metabolic connectivity than young adults in the M band. Furthermore, older adults exhibited significantly stronger unilateral coupling on both prefrontal sides in all E/N/M bands, particularly with a very large effect size in the M band (>1.9). These age-related results clearly support our hypothesis and were well interpreted following neurophysiological principles. The key finding of this paper is that the neurophysiological metrics of uCOP and bCON are highly associated with age and may have the potential to become meaningful features for human brain health and be translatable for future clinical applications, such as the early detection of Alzheimer's disease.

Site-specific effects of 800- and 850-nm forehead transcranial photobiomodulation on prefrontal bilateral connectivity and unilateral coupling in young adults.

Significance: Transcranial photobiomodulation (tPBM) is a noninvasive neuromodulation method that facilitates the improvement of human cognition. However, limited information is available in the literature on the wavelength- and site-specific effects of prefrontal tPBM. Moreover, 2-channel broadband near-infrared spectroscopy (2-bbNIRS) is a new approach for quantifying infra-slow oscillations (ISO; 0.005 to 0.2 Hz) of neurophysiological networks in the resting human brain in vivo. Aim: We aim to prove the hypothesis that the hemodynamic and metabolic activities of the resting prefrontal cortex are significantly modulated by tPBM and that the modulation is wavelength- and site-specific in different ISO bands. Approach: Noninvasive 8-min tPBM with an 800- or 850-nm laser or sham was delivered to either side of the forehead of 26 healthy young adults. A 2-bbNIRS unit was used to record prefrontal ISO activity 7 min before and after tPBM/sham. The measured time series were analyzed in the frequency domain to determine the coherence of hemodynamic and metabolic activities at each of the three ISO frequency bands. Sham-controlled coherence values represent tPBM-induced effects on neurophysiological networks. Results: Prefrontal tPBM by either wavelength and on either lateral side of the forehead (1) increased ipsilateral metabolic-hemodynamic coupling in the endogenic band and (2) desynchronized bilateral activity of metabolism in the neurogenic band and vascular smooth-muscle hemodynamics in the myogenic band. Site-specific effects of laser tPBM were also observed with significant enhancement of bilateral hemodynamic and metabolic connectivity by the right prefrontal 800-nm tPBM. Conclusions: Prefrontal tPBM can significantly modulate neurophysiological networks bilaterally and coupling unilaterally in the human prefrontal cortex. Such modulation effects are site- and wavelength-specific for each ISO band.

Prefrontal cortical connectivity and coupling of infraslow oscillation in the resting human brain: a 2-channel broadband NIRS study.

The resting-state infraslow oscillation (ISO) of the cerebral cortex reflects the neurophysiological state of the human brain. ISO results from distinct vasomotion with endogenic (E), neurogenic (N), and myogenic (M) frequency bands. Quantification of prefrontal ISO in cortical hemodynamics and metabolism in the resting human brain may facilitate the identification of objective features that are characteristic of certain brain disorders. The goal of this study was to explore and quantify the prefrontal ISO of the cortical concentration changes of oxygenated hemoglobin (Δ[HbO]) and redox-state cytochrome c oxidase (Δ[CCO]) as hemodynamic and metabolic activity metrics in all 3 E/N/M bands. Two-channel broadband near-infrared spectroscopy (2-bbNIRS) enabled measurements of the forehead of 26 healthy young participants in a resting state once a week for 5 weeks. After quantifying the ISO spectral amplitude (SA) and coherence at each E/N/M band, several key and statistically reliable metrics were obtained as features: (i) SA of Δ[HbO] at all E/N/M bands, (ii) SA of Δ[CCO] in the M band, (iii) bilateral connectivity of hemodynamics and metabolism across the E and N bands, and (iv) unilateral hemodynamic-metabolic coupling in each of the E and M bands. These features have promising potential to be developed as objective biomarkers for clinical applications in the future.

Puckering the Planar Landscape of Fragments: Design and Synthesis of a 3D Cyclobutane Fragment Library.

Fragment-based drug discovery (FBDD) has a growing need for unique screening libraries. The cyclobutane moiety was identified as an underrepresented yet attractive three-dimensional (3D) scaffold. Synthetic strategies were developed via a key 3-azido-cyclobutanone intermediate, giving potential access to a range of functional groups with accessible growth vectors. A focused set of 33 novel 3D cyclobutane fragments was synthesised, comprising three functionalities: secondary amines, amides, and sulfonamides. This library was designed using Principal Component Analysis (PCA) and an expanded version of the rule of three (RO3), followed by Principal Moment of Inertia (PMI) analysis to achieve both chemical diversity and high 3D character. Cis and trans ring isomers of library members were generated to maximise the shape diversity obtained, while limiting molecular complexity through avoiding enantiomers. Property analyses of the cyclobutane library indicated that it fares favourably against existing synthetic 3D fragment libraries in terms of shape and physicochemical properties.

Photobiomodulation at Different Wavelengths Boosts Mitochondrial Redox Metabolism and Hemoglobin Oxygenation: Lasers vs. Light-Emitting Diodes In Vivo.

Our group previously examined 8 min photobiomodulation (PBM) by 1064 nm laser on the human forearm in vivo to determine its significant effects on vascular hemodynamics and cytochrome c oxidase redox activity. Since PBM uses a wide array of wavelengths, in this paper, we investigated (i) whether different wavelengths of lasers induced different PBM effects, and (ii) if a light-emitting diode (LED) at a similar wavelength to a laser could induce similar PBM effects. A broadband near-infrared spectroscopy (bbNIRS) system was utilized to assess concentration changes in oxygenated hemoglobin (Δ[HbO]) and oxidized cytochrome c oxidase (Δ[oxCCO]) during and after PBM with lasers at 800 nm, 850 nm, and 1064 nm, as well as a LED at 810 nm. Two groups of 10 healthy participants were measured before, during, and after active and sham PBM on their forearms. All results were tested for significance using repeated measures ANOVA. Our results showed that (i) lasers at all three wavelengths enabled significant increases in Δ[HbO] and Δ[oxCCO] of the human forearm while the 1064 nm laser sustained the increases longer, and that (ii) the 810-nm LED with a moderate irradiance (≈135 mW/cm2) induced measurable and significant rises in Δ[HbO] and Δ[oxCCO] with respect to the sham stimulation on the human forearm.

TrueNTH Sexual Recovery Intervention for couples coping with prostate cancer: Randomized controlled trial results.

BACKGROUND: Despite significant sexual dysfunction and distress after localized prostate cancer treatment, patients typically receive only physiologic erectile dysfunction management. The authors performed a randomized controlled trial of an online intervention supporting couples' posttreatment recovery of sexual intimacy. METHODS: Patients treated with surgery, radiation, or combined radiation and androgen deprivation therapy who had partners were recruited and randomized to an online intervention or a control group. The intervention, tailored to treatment type and sexual orientation, comprised 6 modules addressing expectations for sexual and emotional sequelae of treatment, rehabilitation, and guidance toward sexual intimacy recovery. Couples, recruited from 6 sites nationally, completed validated measures at the baseline and 3 and 6 months after treatment. Primary outcome group differences were assessed with t tests for individual outcomes. RESULTS: Among 142 randomized couples, 105 patients (mostly surgery) and 87 partners completed the 6-month survey; this reflected challenges with recruitment and attrition. There were no differences between the intervention and control arms in Patient-Reported Outcomes Measurement Information System Global Satisfaction With Sex Life scores 6 months after treatment (the primary outcome). Three months after treatment, intervention patients and partners reported more engagement in penetrative and nonpenetrative sexual activities than controls. More than 73% of the intervention participants reported high or moderate satisfaction with module content; more than 85% would recommend the intervention to other couples. CONCLUSIONS: Online psychosexual support for couples can help couples to connect and experience sexual pleasure early after treatment despite patients' sexual dysfunction. Participants' high endorsement of the intervention reflects the importance of sexual health support to couples after prostate cancer treatment. LAY SUMMARY: This study tested a web-based program supporting couples' sexual recovery of sexual intimacy after prostate cancer treatment. One hundred forty-two couples were recruited and randomly assigned to the program (n = 60) or to a control group (n = 82). The program did not result in improvements in participants' satisfaction with their sex life 6 months after treatment, but couples in the intervention group engaged in sexual activity sooner after treatment than couples in the control group. Couples evaluated the program positively and would recommend it to others facing prostate cancer treatment.

Local genetic context shapes the function of a gene regulatory network.

Gene expression levels are influenced by multiple coexisting molecular mechanisms. Some of these interactions such as those of transcription factors and promoters have been studied extensively. However, predicting phenotypes of gene regulatory networks (GRNs) remains a major challenge. Here, we use a well-defined synthetic GRN to study in Escherichia coli how network phenotypes depend on local genetic context, i.e. the genetic neighborhood of a transcription factor and its relative position. We show that one GRN with fixed topology can display not only quantitatively but also qualitatively different phenotypes, depending solely on the local genetic context of its components. Transcriptional read-through is the main molecular mechanism that places one transcriptional unit (TU) within two separate regulons without the need for complex regulatory sequences. We propose that relative order of individual TUs, with its potential for combinatorial complexity, plays an important role in shaping phenotypes of GRNs.

The distribution and mitochondrial genotype of the hydroid Aglaophenia latecarinata is correlated with its pelagic Sargassum substrate type in the tropical and subtropical western Atlantic Ocean.

The pelagic brown macroalga Sargassum supports rich biological communities in the tropical and subtropical Atlantic region, including a variety of epiphytic invertebrates that grow on the Sargassum itself. The thecate hydroid Aglaophenia latecarinata is commonly found growing on some, but not all, Sargassum forms. In this study, we examined the relationship between A. latecarinata and its pelagic Sargassum substrate across a broad geographic area over the course of 4 years (2015-2018). The distribution of the most common Sargassum forms that we observed (Sargassum fluitans III and S. natans VIII) was consistent with the existence of distinct source regions for each. We found that A. latecarinata hydroids were abundant on both S. natans VIII and S. fluitans III, and also noted a rare observation of A. latecarinata on S. natans I. For the hydroids on S. natans VIII and S. fluitans III, hydroid mitochondrial genotype was strongly correlated with the Sargassum substrate form. We found significant population genetic structure in the hydroids, which was also consistent with the distributional patterns of the Sargassum forms. These results suggest that hydroid settlement on the Sargassum occurs in type-specific Sargassum source regions. Hydroid species identification is challenging and cryptic speciation is common in the Aglaopheniidae. Therefore, to confirm our identification of A. latecarinata, we conducted a phylogenetic analysis that showed that while the genus Aglaophenia was not monophyletic, all A. latecarinata haplotypes associated with pelagic Sargassum belonged to the same clade and were likely the same species as previously published sequences from Florida, Central America, and one location in Brazil (São Sebastião). A nominal A. latecarinata sequence from a second Brazilian location (Alagoas) likely belongs to a different species.

What Patients and Partners Want in Interventions That Support Sexual Recovery After Prostate Cancer Treatment: An Exploratory Convergent Mixed Methods Study.

INTRODUCTION: Men treated for prostate cancer suffer from treatment-related sexual side effects that adversely affect their relationships and quality of life. AIM: To investigate what prostate cancer survivors and their partners want from a sexual recovery intervention, and whether they consider an online tool acceptable for use in promoting sexual recovery. METHODS: This mixed-methods study included focus groups and interviews with both heterosexual and gay cancer survivors, as well as their partners. Focus groups and interviews probed experiences with treatment, side effects, and support received/needed for sexual recovery. Participants responded to proposed web-based intervention content. Interviews were analyzed with thematic content analysis. Their sexual function was assessed with validated measures. MAIN OUTCOME MEASURES: Acceptability of online tools for promoting sexual recovery was evaluated. RESULTS: Participants included 14 patients and 10 partners (2 male). Patient and partner median age was 62 and 62.5 years, respectively. Treatment ranged from surgery alone to combined radiation and hormonal therapy. Qualitative data analysis yielded 5 main intervention needs: (i) pretreatment discussion of sexual side effects, rehabilitation, emotional impact and realistic expectations, (ii) improved sexual communication within couples, (iii) strategies for promoting sexual intimacy beyond penetrative intercourse, (iv) attentiveness to partners' needs, and (v) access to peer support. Gay men specifically expressed the need for improved provider understanding of their sexuality and experiences. Most considered a web-based approach to be acceptable. CONCLUSION: Patients and partners value both pretreatment preparation for sexual recovery and support for sexual recovery for both after treatment. A web-based approach may help mitigate barriers to access to these support services. Mehta A, Pollack CE, Gillespie T., et. al. What Patients and Partners Want in Interventions That Support Sexual Recovery After Prostate Cancer Treatment: An Exploratory Convergent Mixed Methods Study. Sex Med 2019;7:184-191.

Service user input in pre-registration children's nursing education.

The Nursing and Midwifery Council pre-registration standards include service user involvement in all aspects of the curricula, and the subject has been high on the healthcare agenda for more than a decade. In 2008, service user involvement in a pre-registration children's nursing programme at a UK university was planned, implemented and further developed. The strategy was effective in recruiting and selecting students, but caution is needed to ensure the process is safe for all participants.

Appreciative Inquiry for quality improvement in primary care practices.

PURPOSE: To test the effect of an Appreciative Inquiry (AI) quality improvement strategy on clinical quality management and practice development outcomes. Appreciative inquiry enables the discovery of shared motivations, envisioning a transformed future, and learning around the implementation of a change process. METHODS: Thirty diverse primary care practices were randomly assigned to receive an AI-based intervention focused on a practice-chosen topic and on improving preventive service delivery (PSD) rates. Medical-record review assessed change in PSD rates. Ethnographic field notes and observational checklist analysis used editing and immersion/crystallization methods to identify factors affecting intervention implementation and practice development outcomes. RESULTS: The PSD rates did not change. Field note analysis suggested that the intervention elicited core motivations, facilitated development of a shared vision, defined change objectives, and fostered respectful interactions. Practices most likely to implement the intervention or develop new practice capacities exhibited 1 or more of the following: support from key leader(s), a sense of urgency for change, a mission focused on serving patients, health care system and practice flexibility, and a history of constructive practice change. CONCLUSIONS: An AI approach and enabling practice conditions can lead to intervention implementation and practice development by connecting individual and practice strengths and motivations to the change objective.

A systematic approach to practice assessment and quality improvement intervention tailoring.

BACKGROUND: The ways in which tailored interventions foster sustained improvement in the quality of health care delivery across different practice settings are not well understood. Using the empirically developed Practice Change Model (PCM), we identify and describe assessment and tailoring activities with potential to enhance the fit between proposed interventions and practice settings. METHODS: We obtained quantitative and qualitative data from 2 quality improvement trials conducted in diverse primary care practices in northeast Ohio. A multidisciplinary team used a PCM-based template to identify features of practice assessment and tailoring associated with practices' willingness and ability to change. RESULTS: Our results suggest that intervention tailoring requires assessment of key stakeholders' motivations, external influences, resources and opportunities for change, and the interactions between these factors. Using this information, intervention tailoring then includes seeking and working with key stakeholders, building assets, providing options, keeping change processes flexible, offering feedback, providing exposure to scientific evidence, facilitating group processes, involving new partners, brainstorming, using stories/play acting/humor, assuming a consultant role, reframing, moving meetings off-site, and stepping back or pausing. CONCLUSIONS: A model-driven approach guiding practice assessment enables tailored responses to the unique and emerging conditions that distinguish health care practices and influence implementation of quality management interventions.

Measuring practice capacity for change: a tool for guiding quality improvement in primary care settings.

PURPOSE: Capacity for change, or the ability and willingness to undertake change, is an organizational characteristic with potential to foster quality management in health care. We report on the development and psychometric properties of a quantitative measure of capacity for change for use in primary care settings. METHODS: Following review of previous conceptual and empirical studies, we generated 117 items that assessed organizational structure, climate, and culture. Using information from direct observation and key informant interviews, a research team member rated these items for 15 primary care practices engaged in a quality improvement intervention. Distributional statistics, pairwise correlation analysis, Rasch modeling, and item content review guided item reduction and instrument finalization. Reliability and convergent validity were assessed. RESULTS: Ninety-two items were removed because of limited response distributions and redundancy or because of poor Rasch model fit. The final instrument comprising 25 items had excellent reliability (alpha = .94). A Rasch model-derived capacity for change score correlated well with an independently determined, qualitatively derived summary assessment of each practice's capacity for change (rhoS = 0.82), suggesting good convergent validity. CONCLUSION: We describe a new instrument for quantifying organizational capacity for change in primary care settings. The ability to quantify capacity for change may enable better recognition of practices likely to be successful in their change efforts and those first requiring capacity building prior to change interventions.

Evaluation study to ascertain the impact of the clinical academic coaching role for enhancing student learning experience within a clinical masters education programme.

AIM: To explore the appropriateness of clinical academic coaching role as a tool for enhancing student learning and the development of advanced academic and clinical practice skills for nurses. BACKGROUND: Coaching involves a relationship between individuals characterised by analyzing and communicating mutually understood objectives and motivating others. Coaching is beneficial for developing those entering new positions with higher level responsibilities. METHOD: A two stage evaluation involved analysis of structured questionnaires distributed to students registered for a postgraduate advanced clinical practice programme and ten interviews with students and coaches. Data was analysed to develop understanding of how coaches were experienced by students as an aid to learning. FINDINGS: Data indicates the role supported students through transition and provided learning support at crucial times in the academic journey. Specific skills and behaviours enhanced the coach-student relationship. The coach's understanding of the clinical context was pivotal, as was effective preparation to undertake the coaching role. CONCLUSION: Supporting students to make the transition into advanced practice roles is a prominent issue within current healthcare literature. Clinical coaching enhances learning through a strong and coherent partnership between the student, their practice context and the academic journey.

Correlates of baseline performance do not predict results of an intervention to improve preventive care.

BACKGROUND: Cross-sectional analyses of baseline performance often inform the development of interventions to improve care. An implicit assumption in these studies is that factors associated with better performance at baseline may also be useful in predicting change in performance over time. METHODS: We analyzed data collected from 1997-2002 at 77 practices in Northeast Ohio participating in an intervention to increase evidence-based preventive services delivery (PSD). Spearman's correlation coefficients and multivariable models assessed associations between practice-level characteristics (e.g., organizational structure, objectives, climate, and culture) and baseline PSD, and with final PSD controlling for baseline values. Patterns of associations for both outcomes were inspected for overlap. RESULTS: The mean PSD rate was 36.8% (+/-8.8%) at baseline. This measure increased by an average of 4.9% (+/-6.3%) by the end of the intervention. Of eight practice characteristics correlated with either baseline performance or change from baseline in PSD, only two were common to both: characteristics associated with baseline PSD did not predict final PSD in multivariable models. CONCLUSIONS: Correlates of baseline performance differ from those related to change in performance. Practice assessments that focus on factors associated with change may be more useful in developing and implementing interventions to improve care.

An appreciative inquiry approach to practice improvement and transformative change in health care settings.

Amid tremendous changes and widespread dissatisfaction with the current health care system, many approaches to improve practice have emerged; however, their effects on quality of care have been disappointing. This article describes the application of a new approach to promote organizational improvement and transformation that is built upon collective goals and personal motivations, invites participation at all levels of the organization and connected community, and taps into latent creativity and energy. The essential elements of the appreciative inquiry (AI) process include identification of an appreciative topic and acting on this theme through 4 steps: Discovery, Dream, Design, and Destiny. We describe each step in detail and provide a case study example, drawn from a composite of practices, to highlight opportunities and challenges that may be encountered in applying AI. AI is a unique process that offers practice members an opportunity to reflect on the existing strengths within the practice, leads them to discover what is important, and builds a collective vision of the preferred future. New approaches such as AI have the potential to transform practices, improve patient care, and enhance individual and group motivation by changing the way participants think about, approach, and envision the future.