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Background Uterine fibroids are non-cancerous overgrowths of the smooth muscle in the uterus. As they grow, some cause problems such as heavy menstrual bleeding, pelvic pain, discomfort during sexual intercourse, and rarely pregnancy complications or difficulty becoming pregnant. Multiple treatment options are available. The lack of comparative evidence demonstrating superiority of any one treatment means that choosing the best option is sensitive to individual preferences. Women with fibroids wish to consider treatment trade-offs. Tools known as patient decision aids (PDAs) are effective in increasing patient engagement in the decision-making process. However, the implementation of PDAs in routine care remains challenging. Our aim is to use a multi-component implementation strategy to implement the uterine fibroids Option Grid™ PDAs at five organizational settings in the USA. Methods We will conduct a randomized stepped-wedge implementation study where five sites will be randomized to implement the uterine fibroid Option Grid PDA in practice at different time points. Implementation will be guided by the Consolidated Framework for Implementation Research (CFIR) and Normalization Process Theory (NPT). There will be a 6-month pre-implementation phase, a 2-month initiation phase where participating clinicians will receive training and be introduced to the Option Grid PDAs (available in text, picture, or online formats), and a 6-month active implementation phase where clinicians will be expected to use the PDAs with patients who are assigned female sex at birth, are at least 18 years of age, speak fluent English or Spanish, and have new or recurrent symptoms of uterine fibroids. We will exclude postmenopausal patients. Our primary outcome measure is the number of eligible patients who receive the Option Grid PDAs. We will use logistic and linear regression analyses to compare binary and continuous quantitative outcome measures (including survey scores and Option Grid use) between the pre- and active implementation phases while adjusting for patient and clinician characteristics. Discussion This study may help identify the factors that impact the implementation and sustained use of a PDA in clinic workflow from various stakeholder perspectives while helping patients with uterine fibroids make treatment decisions that align with their preferences. Trial registration Clinicaltrials.gov , NCT03985449. Registered 13 July 2019, https://clinicaltrials.gov/ct2/show/NCT03985449

Alcohol misuse is a common and well-documented source of morbidity and mortality. Brief primary care alcohol counseling has been shown to benefit patients with alcohol misuse. To describe alcohol-related discussions between primary care providers and patients who screened positive for alcohol misuse. An exploratory, qualitative analysis of audiotaped primary care visits containing discussions of alcohol use. Participants were 29 male outpatients at a Veterans Affairs (VA) General Internal Medicine Clinic who screened positive for alcohol misuse and their 14 primary care providers, all of whom were participating in a larger quality improvement trial. Audiotaped visits with any alcohol-related discussion were transcribed and coded using grounded theory and conversation analysis, both qualitative research techniques. Three themes were identified: (1) patients disclosed information regarding their alcohol use, but providers often did not explore these disclosures; (2) advice about alcohol use was typically vague and/or tentative in contrast to smoking-related advice, which was more common and usually more clear and firm; and (3) discomfort on the part of the provider was evident during alcohol-related discussions. Generalizability of findings from this single-site VA study is unknown. Findings from this single site study suggest that provider discomfort and avoidance are important barriers to evidence-based brief alcohol counseling. Further investigation into current alcohol counseling practices is needed to determine whether these patterns extend to other primary care settings, and to inform future educational efforts.

OBJECTIVE: This study describes primary care discussions with patients who screened positive for at‐risk drinking. In addition, discussions about alcohol use from 2 clinic firms, one with a provider‐prompting intervention, are compared. DESIGN: Cross‐sectional analyses of audiotaped appointments collected over 6 months. PARTICIPANTS AND SETTING: Male patients in a VA general medicine clinic were eligible if they screened positive for at‐risk drinking and had a general medicine appointment with a consenting provider during the study period. Participating patients (N = 47) and providers (N = 17) were enrolled in 1 of 2 firms in the clinic (Intervention or Control) and were blinded to the study focus. INTERVENTION: Intervention providers received patient‐specific results of positive alcohol‐screening tests at each visit. MEASURES AND MAIN RESULTS: Of 68 visits taped, 39 (57.4%) included any mention of alcohol. Patient and provider utterances during discussions about alcohol use were coded using Motivational Interviewing Skills Codes. Providers contributed 58% of utterances during alcohol‐related discussions with most coded as questions (24%), information giving (23%), or facilitation (34%). Advice, reflective listening, and supportive or affirming statements occurred infrequently (5%, 3%, and 5%, of provider utterances respectively). Providers offered alcohol‐related advice during 21% of visits. Sixteen percent of patient utterances reflected “resistance” to change and 12% reflected readiness to change. On average, Intervention providers were more likely to discuss alcohol use than Control providers (82.4% vs 39.6% of visits; P = .026). CONCLUSIONS: During discussions about alcohol, general medicine providers asked questions and offered information, but usually did not give explicit alcohol‐related advice. Discussions about alcohol occurred more often when providers were prompted.

This study describes primary care discussions with patients who screened positive for at-risk drinking. In addition, discussions about alcohol use from 2 clinic firms, one with a provider-prompting intervention, are compared. Cross-sectional analyses of audiotaped appointments collected over 6 months. Male patients in a VA general medicine clinic were eligible if they screened positive for at-risk drinking and had a general medicine appointment with a consenting provider during the study period. Participating patients ( N = 47) and providers ( N = 17) were enrolled in 1 of 2 firms in the clinic (Intervention or Control) and were blinded to the study focus. Intervention providers received patient-specific results of positive alcohol-screening tests at each visit. Of 68 visits taped, 39 (57.4%) included any mention of alcohol. Patient and provider utterances during discussions about alcohol use were coded using Motivational Interviewing Skills Codes. Providers contributed 58% of utterances during alcohol-related discussions with most coded as questions (24%), information giving (23%), or facilitation (34%). Advice, reflective listening, and supportive or affirming statements occurred infrequently (5%, 3%, and 5%, of provider utterances respectively). Providers offered alcohol-related advice during 21% of visits. Sixteen percent of patient utterances reflected \"resistance\" to change and 12% reflected readiness to change. On average, Intervention providers were more likely to discuss alcohol use than Control providers (82.4% vs 39.6% of visits; P =.026). During discussions about alcohol, general medicine providers asked questions and offered information, but usually did not give explicit alcohol-related advice. Discussions about alcohol occurred more often when providers were prompted.

BACKGROUND: Alcohol misuse is a common and well‐documented source of morbidity and mortality. Brief primary care alcohol counseling has been shown to benefit patients with alcohol misuse. OBJECTIVE: To describe alcohol‐related discussions between primary care providers and patients who screened positive for alcohol misuse. DESIGN: An exploratory, qualitative analysis of audiotaped primary care visits containing discussions of alcohol use. PARTICIPANTS: Participants were 29 male outpatients at a Veterans Affairs (VA) General Internal Medicine Clinic who screened positive for alcohol misuse and their 14 primary care providers, all of whom were participating in a larger quality improvement trial. MEASUREMENTS: Audiotaped visits with any alcohol‐related discussion were transcribed and coded using grounded theory and conversation analysis, both qualitative research techniques. RESULTS: Three themes were identified: (1) patients disclosed information regarding their alcohol use, but providers often did not explore these disclosures; (2) advice about alcohol use was typically vague and/or tentative in contrast to smoking‐related advice, which was more common and usually more clear and firm; and (3) discomfort on the part of the provider was evident during alcohol‐related discussions. LIMITATIONS: Generalizability of findings from this single‐site VA study is unknown. CONCLUSION: Findings from this single site study suggest that provider discomfort and avoidance are important barriers to evidence‐based brief alcohol counseling. Further investigation into current alcohol counseling practices is needed to determine whether these patterns extend to other primary care settings, and to inform future educational efforts.

The purpose of the study was to examine the relationship between spirituality, existentialism and positive adult adjustment. The study specifically examined “hope” as a key aspect to positive coping and its counterpart, “hopelessness” as a significant aspect of negative coping. The study also considered life stress, and its impact on coping. Because personality factors often are considered when examining coping, the specific personality factor of “absorption” or “openness to experience” was included. This factor was chosen because it is sometimes associated with the impact of life stress on individuals. Data collection was conducted among 60 adults of various religious background and practice. The Spiritual Well Being Scale with subscales, (Religiousness and Existentialism) was administered along with the Tellegen Absorption Scale, the Holmes Rahe Social Readjustment scale, and the Beck Hopelessness Scale. The results showed a statistically significant correlation (r=.66) between spiritual well-being and lower levels of hopelessness. The results also indicated that higher reported stress was not significantly correlated with either hopelessness or higher spiritual well being. Interestingly, the personality factor of “absorption” was not correlated with higher spiritual or hopelessness, however, there was a significant association (r=.26) between absorption and life stress.

Selective neuronal vulnerability to protein aggregation is found in many neurodegenerative diseases including Alzheimer’s disease (AD). Understanding the molecular origins of this selective vulnerability is, therefore, of fundamental importance. Tau protein aggregates have been found in Wolframin (WFS1)-expressing excitatory neurons in the entorhinal cortex, one of the earliest affected regions in AD. The role of WFS1 in Tauopathies and its levels in tau pathology-associated neurodegeneration, however, is largely unknown. Here we report that WFS1 deficiency is associated with increased tau pathology and neurodegeneration, whereas overexpression of WFS1 reduces those changes. We also find that WFS1 interacts with tau protein and controls the susceptibility to tau pathology. Furthermore, chronic ER stress and autophagy-lysosome pathway (ALP)-associated genes are enriched in WFS1-high excitatory neurons in human AD at early Braak stages. The protein levels of ER stress and autophagy-lysosome pathway (ALP)-associated proteins are changed in tau transgenic mice with WFS1 deficiency, while overexpression of WFS1 reverses those changes. This work demonstrates a possible role for WFS1 in the regulation of tau pathology and neurodegeneration via chronic ER stress and the downstream ALP. Our findings provide insights into mechanisms that underpin selective neuronal vulnerability, and for developing new therapeutics to protect vulnerable neurons in AD.

CRISPR/Cas9-based genome editing has yet to be reported in species of the Platyhelminthes. We tested this approach by targeting omega-1 (ω1) of Schistosoma mansoni as proof of principle. This secreted ribonuclease is crucial for Th2 polarization and granuloma formation. Schistosome eggs were exposed to Cas9 complexed with guide RNA complementary to ω1 by electroporation or by transduction with lentiviral particles. Some eggs were also transfected with a single stranded donor template. Sequences of amplicons from gene-edited parasites exhibited Cas9-catalyzed mutations including homology directed repaired alleles, and other analyses revealed depletion of ω1 transcripts and the ribonuclease. Gene-edited eggs failed to polarize Th2 cytokine responses in macrophage/T-cell co-cultures, while the volume of pulmonary granulomas surrounding ω1-mutated eggs following tail-vein injection into mice was vastly reduced. Knock-out of ω1 and the diminished levels of these cytokines following exposure showcase the novel application of programmed gene editing for functional genomics in schistosomes. Schistosomiasis is a tropical disease that can cause serious health problems, including damage to the liver and kidneys, infertility and bladder cancer. Nearly a quarter billion people are currently infected, mostly in poor regions of sub-Saharan Africa, the Philippines and Brazil. A freshwater worm known as Schistosoma mansoni causes the disease. These parasites enter the human body by burrowing into the skin; once in the bloodstream, they move to various organs where they rapidly start to reproduce. Their eggs release several molecules, including a protein known as omega-1 ribonuclease, which can damage the surrounding tissues. A gene editing technique called CRISPR/Cas9 allows scientists to precisely target and then deactivate the genetic information a cell needs to produce a given protein. While the tool has been used in other species before, it was unknown if it could be applied to S. mansoni. Here, Ittiprasert et al. harnessed CRISPR/Cas9 to deactivate the gene that codes for omega-1 ribonuclease and create parasites that do not produce the protein, or only very little of it. The experiments showed that mice infected with the gene-edited worm eggs displayed far fewer symptoms of schistosomiasis compared to those that carry the non-edited parasites. Alongside this work, Arunsan et al. used CRISPR/Cas9 to inactivate a gene in another species of worm that can cause liver cancer in humans. Together, these findings demonstrate for the first time that the gene editing method can be adapted for use in parasitic flatworms, which are a major public health problem in tropical climates. This tool should help scientists understand how the parasites invade and damage our bodies, and provide new ideas for treatment and disease control.

Salutary responses to adeno-associated viral (AAV) gene therapy have been reported in the mouse model of Sandhoff disease (SD), a neurodegenerative lysosomal storage disease caused by deficiency of β-N-acetylhexosaminidase (Hex). While untreated mice reach the humane endpoint by 4.1 months of age, mice treated by a single intracranial injection of vectors expressing human hexosaminidase may live a normal life span of 2 years. When treated with the same therapeutic vectors used in mice, two cats with SD lived to 7.0 and 8.2 months of age, compared with an untreated life span of 4.5 ± 0.5 months (n = 11). Because a pronounced humoral immune response to both the AAV1 vectors and human hexosaminidase was documented, feline cDNAs for the hexosaminidase α- and β-subunits were cloned into AAVrh8 vectors. Cats treated with vectors expressing feline hexosaminidase produced enzymatic activity >75-fold normal at the brain injection site with little evidence of an immune infiltrate. Affected cats treated with feline-specific vectors by bilateral injection of the thalamus lived to 10.4 ± 3.7 months of age (n = 3), or 2.3 times as long as untreated cats. These studies support the therapeutic potential of AAV vectors for SD and underscore the importance of species-specific cDNAs for translational research.

The organizers of the 2014 US National Climate Assessment (NCA) made a concerted effort to reach out to and collaborate with Indigenous peoples, resulting in the most comprehensive information to date on climate change impacts to Indigenous peoples in a US national assessment. Yet, there is still much room for improvement in assessment processes to ensure adequate recognition of Indigenous perspectives and Indigenous knowledge systems. This article discusses the process used in creating the Indigenous Peoples, Land, and Resources NCA chapter by a team comprised of tribal members, agencies, academics, and non-governmental organizations, who worked together to solicit, collect, and synthesize traditional knowledges and data from a diverse array of Indigenous communities across the US. It also discusses the synergy and discord between traditional knowledge systems and science and the emergence of cross-cutting issues and vulnerabilities for Indigenous peoples. The challenges of coalescing information about climate change and its impacts on Indigenous communities are outlined along with recommendations on the types of information to include in future assessment outputs. We recommend that future assessments – not only NCA, but other relevant local, regional, national, and international efforts aimed at the translation of climate information and assessments into meaningful actions – should support integration of Indigenous perspectives in a sustained way that builds respectful relationships and effectively engages Indigenous communities. Given the large number of tribes in the US and the current challenges and unique vulnerabilities of Indigenous communities, a special report focusing solely on climate change and Indigenous peoples is warranted.