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BackgroundNo definitive, antemortem diagnostic test for canine degenerative myelopathy (DM) is available. Phosphorylated neurofilament heavy (pNF-H) is a promising biomarker for nervous system diseases.Hypothesis/objectiveCerebrospinal fluid (CSF) and serum pNF-H is a detectable biological marker for diagnosis of canine DM.AnimalsFifty-three DM-affected, 27 neurologically normal, 7 asymptomatic at-risk, and 12 DM mimic dogs.MethodsArchived CSF and serum pNF-H concentrations were determined by a commercially available ELISA. A receiver-operating characteristic (ROC) curve was generated with CSF values.ResultsCompared with old control dogs, median CSF pNF-H concentration was increased in all stages of DM; old dogs 5.1 ng/mL (interquartile range [IQR] 1.4-9.3) versus DM stage 1 23.9 ng/mL (IQR 20.8-29.6; P < .05) versus DM stage 2 36.8 ng/mL (IQR 22.9-51.2; P < .0001) versus DM stage 3 25.2 ng/mL (IQR 20.2-61.8; P < .001) versus DM stage 4 38.0 ng/mL (IQR 11.6-59.9; P < .01). Degenerative myelopathy stage 1 dogs had increased median CSF pNF-H concentrations compared with asymptomatic, at-risk dogs (3.4 ng/mL [IQR 1.5-10.9; P < .01]) and DM mimics (6.6 ng/mL [IQR 3.0-12.3; P < .01]). CSF pNF-H concentration >20.25 ng/mL was 80.4% sensitive (confidence interval [CI] 66.09-90.64%) and 93.6% specific (CI 78.58-99.21%) for DM. Area under the ROC curve was 0.9467 (CI 0.92-0.9974). No differences in serum pNF-H concentration were found between control and DM-affected dogs.Conclusions and clinical importancepNF-H concentration in CSF is a sensitive biomarker for diagnosis of DM. Although there was high specificity for DM in this cohort, further study should focus on a larger cohort of DM mimics, particularly other central and peripheral axonopathies.

Models that explain preventive behaviors, such as colorectal cancer (CRC) screening, do not account for social and cultural factors relevant to African Americans. This exploratory study examined the relationship between socio-cultural factors (e.g., traditional acculturative strategy, group-based medical mistrust, physician ethnicity, and group-level perceptions of susceptibility) and perceived benefits, perceived barriers, and CRC screening intentions among African Americans ( N = 198; Age: M = 59.7, SD = 9.9; 65% female; 44% household income $50,000+). Hierarchical multiple regression was used to test the following models with perceived benefits, perceived barriers, and screening intentions as the outcomes: (a) traditional acculturative strategy x medical mistrust; (b) physician's ethnicity x medical mistrust; (c) group susceptibility x medical mistrust; and (d) group susceptibility x traditional acculturative strategy. Results revealed that perceiving high group susceptibility while being both more culturally traditional and less mistrustful was associated with more perception of screening benefits. Greater intention to be screened was associated with perceiving high group susceptibility while having a more traditional cultural orientation and low levels of mistrust in those with African American physicians. These results suggest that it may be beneficial to include these social and cultural factors in behavioral interventions to increase CRC screening among African Americans. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine the role of physical activity (PA) companions in supporting PA participation among African American women. METHODS: Data were collected through in-depth interviews and focus groups. Fifteen physically active African American women participated in the study. Grounded theory data analysis techniques were used to develop a taxonomy depicting roles of PA companions for African American women. RESULTS: PA companions functioned in 4 different roles: motivational, social, facilitative, and instructional. Supportive behaviors associated with each role were also elucidated. CONCLUSIONS: These findings provide an understanding for the function of companions in sustaining active lifestyle that can be used to inform intervention development. [ABSTRACT FROM AUTHOR]

The use of complementary and alternative medicine (CAM) is common among many rural residents but little is known about its use among the Amish. The aim of this study was to determine the prevalence of CAM therapy use among an Amish community and compare it to a rural non-Amish population. Data were taken from a cancer-related lifestyle cross-sectional individual interview survey conducted among Amish and non-Amish residents of Ohio Appalachia. Amish adults (62 males, 72 females) were compared to non-Amish adults (64 males, 90 females) in terms of CAM therapy use and utilization of mainstream healthcare services. Prior use of any CAM therapy was highly prevalent among both Amish (males: 98%, female: 100%) and non-Amish (males: 89%, females: 98%) participants. CAM therapies for which the prevalence was significantly higher among Amish participants for both genders included chiropractic therapy (males: 84% vs. 61%, p=0.005; females: 90% vs. 57%, p<0.001) and reflexology (males: 35% vs. 5%, p<0.001; females: 53% vs. 13%, p<0.001). Few differences in the use of mainstream healthcare services were found between Amish and non-Amish participants. While CAM therapy use was widespread among both Amish and non-Amish participants, the Amish generally reported higher levels of prior use. These findings underscore the importance of physicians and nurses collecting information on CAM therapies when treating patients in this region, particularly Amish patients. [ABSTRACT FROM AUTHOR]

Background: Little is known about cancer surveillance (mammography, clinical breast examination, and pelvic examination) behaviors in long-term (9-16 years) breast cancer survivors. This report describes the relation of these behaviors to demographic and clinical characteristics, psychological symptoms, body satisfaction, and social support.Methods: Survivors who had participated in Cancer and Leukemia Group B treatment Trial 8541 completed a survey that included questions on breast cancer surveillance and pelvic examination, psychological well being, body satisfaction, and social support.Results: The participation rate was 78% and included 245 breast cancer survivors. Survivors (n = 107; 44%) reported completing breast cancer surveillance (mammography and clinical breast examination) and completing pelvic examination (n = 162; 68%) within recommended guidelines. There were no significant associations between breast cancer surveillance and breast cancer anxiety, depression, stressful life events, body satisfaction, social support, or demographic characteristics. Survivors within recommended guidelines for pelvic examinations were younger (P = .05), married (P = .003), had health insurance (P = .004), and had lower depression scores (P = .005) than survivors who underused or overused pelvic examination. In addition, survivors within recommended pelvic examination guidelines had significantly lower levels of breast cancer anxiety (P = .03) compared with survivors who underused pelvic examination.Conclusions: Many long-term breast cancer survivors were not within recommended cancer surveillance guidelines. Private health insurance was associated with following recommendations for pelvic examinations, although such a relation did not exist for breast cancer surveillance. The results of this study have implications for the development of educational programs to improve cancer surveillance among the growing population of long-term breast cancer survivors. [ABSTRACT FROM AUTHOR]

Regular physical activity is linked to a reduced risk of obesity and chronic disease. African American women bear a disproportionate burden from these conditions and many do not get the recommended amount of physical activity. Long-term success of interventions to initiate and maintain a physically active lifestyle among African American women has not been realized. By clearly elucidating the process of physical activity adoption and maintenance, effective programming could be implemented to reduce African American women's burden from chronic conditions. In-depth interviews were conducted with physically active African American women. Grounded theory, a rigorous qualitative research method used to develop theoretical explanation of human behavior grounded in data collected from those exhibiting that behavior, was used to guide the data collection and analysis process. Data derived inductively from the interviews and focus groups guided the development of a behavioral framework explaining the process of physical activity evolution. [ABSTRACT FROM AUTHOR]

We examined the influence of social and cultural contexts on participation in recommended levels of physical activity (PA) among African American women using a grounded theory approach. Data were collected through in-depth interviews and focus groups with 15 physically active African American women. Participants described social and cultural factors that served as challenges for participation in PA. Of particular importance, participants discussed their strategies for overcoming these challenges to initiate and maintain an active lifestyle. Strategies emerged to address three main areas: lack of PA exposure, PA norms and beliefs, and hair maintenance. Understanding contextually appropriate strategies to assist African American women in long-term PA maintenance will help inform effective health promotion efforts to reduce the burden of sedentary lifestyle and chronic disease in this community of women. [ABSTRACT FROM AUTHOR]

Background: Little is known about the difference between the concerns of men and women prior to undergoing diagnostic tests for cancer. Methods: A convenience sample of 129 outpatients completed a survey. Results: No statistically significant differences were found between male and female patients; however, patients evaluated for gender-specific cancers reported a significantly (P < .01) higher mean score for concerns related to sexuality, reproductive ability, and intimate relationships. Almost half (46%) of the patients reported not receiving any or not enough information before the procedure. Conclusions: Men and women have similar concerns; however, there are significant differences in the concerns of patients undergoing a procedure for a gender-specific versus a non-gender-specific cancer. Some patients reported inadequate procedural information, suggesting that improvements are needed in communication and health education efforts. [ABSTRACT FROM AUTHOR]

Some genetic counselors (GCs) may find theories, models, and frameworks (TMFs) useful in clinical skills selection and when reflecting on or evaluating genetic counseling practice. This paper aims to demonstrate how TMFs can be used to postulate how different skills may impact patients'/clients' decisions, behaviors, and outcomes and consider how multiple TMFs can inform the use of various skills or strategies to achieve different goals. Additionally, we provide examples of TMFs that may help GCs in nonclinical aspects of their work, such as implementing and evaluating new interventions or service delivery models. To guide the selection of appropriate TMFs, we provide a set of questions to consider and include examples of skills and approaches that align with different TMFs. While TMFs provide a structured approach and valuable guidance that may help advance genetic counseling practice, they have certain limitations. Additional research is necessary to determine the effectiveness of using TMFs to guide clinical practice and improve patient/client outcomes., (© 2024 National Society of Genetic Counselors.)

Background: Despite the promise of mail-based human papillomavirus (HPV) self-collection programs for increasing cervical cancer screening, few have been evaluated in the United States. We report the results of a mail-based HPV self-collection program for underscreened women living in Appalachia., Methods: We conducted a group randomized trial during 2021-2022 in the Appalachian regions of Kentucky, Ohio, Virginia, and West Virgnia. Participants were women ages 30-64 who were underscreened for cervical cancer and from a participating health system. Participants in the intervention group (n=464) were mailed an HPV self-collection kit followed by telephone-based patient navigation (if needed), and participants in the usual care group (n=338) were mailed a reminder letter to get a clinic-based cervical cancer screening test. Generalized linear mixed models compared cervical cancer screening between study groups., Results: Overall, 14.9% of participants in the intervention group and 5.0% of participants in the usual care group were screened for cervical cancer. The mail-based HPV self-collection intervention increased cervical cancer screening compared to the usual care group (OR=3.30, 95% CI: 1.90-5.72, p=0.005). One or more high-risk HPV types were detected in 10.5% of the returned HPV self-collection kits. Among participants in the intervention group who patient navigators attempted to contact, 44.2% were successfully reached., Conclusions: HPV self-collection increased cervical cancer screening, and future efforts are needed to determine how to optimize such programs, including the delivery of patient navigation services., Impact: Mail-based HPV self-collection programs are a viable strategy for increasing cervical cancer screening among underscreened women living in Appalachia.

Background: Insulin efsitora alfa (efsitora) is a once-weekly basal insulin. This phase 3 study aimed to assess the efficacy and safety of efsitora compared with insulin degludec (degludec) in adults with type 1 diabetes., Methods: This randomised, 52-week, parallel-design, open-label, treat-to-target non-inferiority study conducted at 82 global health-care centres, randomly assigned (1:1) adults (ie, those aged ≥18 years) with type 1 diabetes glycated haemoglobin A 1c (HbA 1c ) 7·0-10·0% (53·0-85·8 mmol/mol) to efsitora (n=343) or, degludec (n=349), both in combination with insulin lispro. The primary endpoint was the change in HbA 1c from baseline to week-26 (non-inferiority margin=0·4%). The trial was registered at ClinicalTrials.gov (NCT05463744) and is completed., Findings: Between Aug 12, 2022, and May 7, 2024, of 893 participants enrolled, 692 (77%) participants were randomly assigned to once-weekly efsitora or once-daily degludec, and 623 (90%) participants completed the study. Mean HbA 1c decreased from 7·88% (62·66 mmol/mol) at baseline to 7·41% (57·5 mmol/mol) at week 26 with efsitora and from 7·94% (63·3 mmol/mol) at baseline to 7·36% (56·9 mmol/mol) at week 26 with degludec. Mean HbA 1c change from baseline to week 26 was -0·51% with efsitora and -0·56% with degludec (estimated treatment difference 0·052%, 95% CI -0·077 to 0·181; p=0·43), confirming a non-inferiority margin of 0·4% for efsitora compared with degludec. Rates of combined level 2 (<54 mg/dL [3·0 mmol/L]) or level 3 severe hypoglycaemia were higher with efsitora compared with degludec (14·03 vs 11·59 events per patient year of exposure; estimated rate ratio 1·21, 95% CI 1·04 to 1·41; p=0·016) during weeks 0-52, with the highest rates during weeks 0-12. Severe hypoglycaemia incidence was higher with efsitora (35 [10%] of 343) versus degludec (11 [3%] of 349) during weeks 0-52. Overall incidence of treatment-emergent adverse events was similar across treatment groups. One death not related to the study treatment occurred in the degludec group., Interpretation: In adults with type 1 diabetes, once-weekly efsitora showed non-inferior HbA 1c reduction compared with daily insulin degludec. Higher rates of combined level 2 or level 3 hypoglycaemia and greater incidence of severe hypoglycaemia in participants treated with efsitora compared with participants treated with degludec might suggest the need for additional evaluation of efsitora dose initiation and optimisation in people with type 1 diabetes., Funding: Eli Lilly and Company., Competing Interests: Declaration of interests RMB has received research support from, consulted, or has been on a scientific advisory board for Abbott Diabetes Care, Ascensia, Bigfoot Biomedical, CeQur, Dexcom, Eversense, Hygieia, Insulet, Eli Lilly and Company, Medtronic, Novo Nordisk, Onduo, Roche Diabetes Care, Sanofi, Tandem Diabetes Care, United Healthcare, Vertex Pharmaceutical, and Zealand Pharma. His technology research is funded in part by the National Institute of Diabetes and Digestive and Kidney Diseases and Helmsley Charitable Trust. RMB's employer, non-profit HealthPartners Institute, contracts him for his services, and no personal income from any of these activities goes directly to him. RSW has participated in multicentre clinical trials, through her institution, sponsored by Eli Lilly and Company, Insulet, Tandem, Amgen, MannKind, NovoNordisk, Wolters Kluwer, and Diasome, and has used Dexcom devices obtained at reduced cost in clinical research studies. CM serves or has served on advisory panels for Novo Nordisk, Sanofi, Eli Lilly and Company, Dexcom, Boehringer Ingelheim, Bayer, Roche, Medtronic, Imcyse, Insulet, Biomea Fusion, ActoBio Therapeutics, AstraZeneca, and Vertex. Financial compensation for these activities has been received by KU Leuven; KU Leuven has received research support for CM from Medtronic, Novo Nordisk, Sanofi, and ActoBio Therapeutics. CM serves or has served on the speaker's bureau for Novo Nordisk, Sanofi, Eli Lilly and Company, Medtronic, and Boehringer Ingelheim. Financial compensation for these activities has been received by KU Leuven. YO has received speaker's bureau fees from Eli Lilly, Novo Nordisk, and Sumitomo Pharma. AMC, MLK, MCC, and VV are employees and shareholders of Eli Lilly and Company., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Purpose: To assess the comparative effectiveness of a tailored, interactive digital video disc (DVD) intervention versus DVD plus patient navigation (PN) intervention versus usual care (UC) on the uptake of colorectal cancer (CRC) screening among females living in Midwest rural areas., Methods: As part of a larger study, 663 females (ages 50-74) living in rural Indiana and Ohio and not up-to-date (UTD) with CRC screening at baseline were randomized to one of three study groups. Demographics , health status/history, and beliefs and attitudes about CRC screening were measured at baseline. CRC screening was assessed at baseline and 12 months from medical records and self-report. Multivariable logistic regression was used to determine whether females in each group were UTD for screening and which test they completed., Results: Adjusted for covariates, females in the DVD plus PN group were 3.5× more likely to complete CRC screening than those in the UC group (odds ratio [OR] 3.62; 95% confidence interval [CI]: 2.09, 6.47) and baseline intention to receive CRC screening (OR 3.45, CI: 2.21,5.42) at baseline. Adjusting for covariates, there was no difference by study arm whether females who became UTD for CRC screening chose to complete a colonoscopy or fecal occult blood test/fecal immunochemical test., Conclusions: Many females living in the rural Midwest are not UTD for CRC screening. A tailored intervention that included an educational DVD and PN improved knowledge, addressed screening barriers, provided information about screening test options, and provided support was more effective than UC and DVD-only to increase adherence to recommended CRC screening., (© 2024 The Authors. The Journal of Rural Health published by Wiley Periodicals LLC on behalf of National Rural Health Association.)

Background: Human patients with Ehlers-Danlos syndrome (EDS) are categorized into subtypes based on causative genetic variants and phenotypes. The classical form of EDS, primarily caused by variants in COL5A1 or COL5A2, is a very common subtype in people but is poorly characterized in dogs., Objective: Describe likely causal COL5A1 variants in dogs with classical EDS, summarize clinical histories, discuss potential disease mechanisms, and draw conclusions about disease prognosis., Animals: Seven client-owned dogs that exhibited clinical signs of classical EDS., Methods: Clinical information was recorded from medical records and communication with attending veterinarians and dog owners. To identify potential causal gene sequence variants whole-genome sequence analyses (n = 6) or Sanger sequencing (n = 1) were performed on DNA isolated from the probands. Pathological abnormalities in skin biopsy samples were assessed using histology and electron microscopy in 3 dogs., Results: Six distinct heterozygous COL5A1 sequence variants were identified. The most common clinical signs included fragile skin (n = 7), hyperextensible skin (n = 7), joint hypermobility (n = 6), and atrophic scars (n = 5). The median age at last follow-up or death was 12 years (range, 6.5-14 years). Ultrastructural abnormalities in dermal collagen differed among dogs with different COL5A1 variants., Conclusion and Clinical Importance: We describe the genotypic and phenotypic spectrum of the classical subtype of EDS by identifying 6 novel COL5A1 variants in conjunction with detailed clinical histories that included long-term follow-up information in 7 dogs., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

The magnitude of suffering on both the Israeli and Palestinian sides of the current war is beyond comprehension. Political agendas, misinformation and bias related to the conflict are being seen far too frequently in healthcare and medical academia. We believe it is time for healthcare professionals to redirect our attention away from politics and use our medical training to advocate for peace, care, and the welfare of all people, regardless of which side of the conflict they fall into. Politics in the workplace, particularly when disseminated information is divisive and, at times, based on opinion rather than fact, risks significant harm to patients, their families, and healthcare staff, as well as to institutional reputation. If we genuinely care for the well-being of patients and staff, we must lead by example and prevent healthcare systems and medical journals from being hijacked by politics.

A 23-month-old neutered male dog of unknown ancestry presented with a history of progressive neurological signs that included anxiety, cognitive impairment, tremors, seizure activity, ataxia, and pronounced visual impairment. The clinical signs were accompanied by global brain atrophy. Due to progression in the severity of disease signs, the dog was euthanized at 26 months of age. An examination of the tissues collected at necropsy revealed dramatic intracellular accumulations of autofluorescent inclusions in the brain, retina, and cardiac muscle. The inclusions were immunopositive for subunit c of mitochondrial ATP synthase, and their ultrastructural appearances were similar to those of lysosomal storage bodies that accumulate in some neuronal ceroid lipofuscinosis (NCL) diseases. The dog also exhibited widespread neuroinflammation. Based on these findings, the dog was deemed likely to have suffered from a form of NCL. A whole genome sequence analysis of the proband's DNA revealed a homozygous C to T substitution that altered the intron 3-exon 4 splice site of CLN6 . Other mutations in CLN6 cause NCL diseases in humans and animals, including dogs. The CLN6 protein was undetectable with immunolabeling in the tissues of the proband. Based on the clinical history, fluorescence and electron-microscopy, immunohistochemistry, and molecular genetic findings, the disorder in this dog was classified as an NCL resulting from the absence of the CLN6 protein. Screening the dog's genome for a panel of breed-specific polymorphisms indicated that its ancestry included numerous breeds, with no single breed predominating. This suggests that the CLN6 disease variant is likely to be present in other mixed-breed dogs and at least some ancestral breeds, although it is likely to be rare since other cases have not been reported to date.

Objective: To review mindfulness-based interventions (MBIs) tested in randomized controlled trials (RCT) across the cancer continuum., Data Source: Articles identified in PubMed, CINAHL, Web of Science, PsycINFO, and Embase., Study Inclusion and Exclusion Criteria: Two independent reviewers screened articles for: (1) topic relevance; (2) RCT study design; (3) mindfulness activity; (4) text availability; (5) country (United States); and (6) mindfulness as the primary intervention component., Data Extraction: Twenty-eight RCTs met the inclusion criteria. Data was extracted on the following variables: publication year, population, study arms, cancer site, stage of cancer continuum, participant demographic characteristics, mindfulness definition, mindfulness measures, mindfulness delivery, and behavioral theory., Data Synthesis: We used descriptive statistics and preliminary content analysis to characterize the data and identify emerging themes., Results: A definition of mindfulness was reported in 46% of studies and 43% measured mindfulness. Almost all MBIs were tested in survivorship (50%) or treatment (46%) stages of the cancer continuum. Breast cancer was the focus of 73% of cancer-site specific studies, and most participants were non-Hispanic white females., Conclusion: The scoping review identified 5 themes: (1) inconsistency in defining mindfulness; (2) differences in measuring mindfulness; (3) underrepresentation of racial/ethnic minorities; (4) underrepresentation of males and cancer sites other than breast; and (5) the lack of behavioral theory in the design, implementation, and evaluation of the MBI., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Up to 50% of people scheduled for screening colonoscopy do not complete this test and no studies have focused on minority and low-income populations. Interventions are needed to improve colorectal cancer (CRC) screening knowledge, reduce barriers, and provide alternative screening options. Patient navigation (PN) and tailored interventions increase CRC screening uptake, however there is limited information comparing their effectiveness or the effect of combining them., Purpose: Compare the effectiveness of two interventions to increase CRC screening among minority and low-income individuals who did not attend their screening colonoscopy appointment-a mailed tailored digital video disc (DVD) alone versus the mailed DVD plus telephone-based PN compared to usual care., Methods: Patients (n = 371) aged 45-75 years at average risk for CRC who did not attend a screening colonoscopy appointment were enrolled and were randomized to: (i) a mailed tailored DVD; (ii) the mailed DVD plus phone-based PN; or (iii) usual care. CRC screening outcomes were from electronic medical records at 12 months. Multivariable logistic regression analyses were used to study intervention effects., Results: Participants randomized to tailored DVD plus PN were four times more likely to complete CRC screening compared to usual care and almost two and a half times more likely than those who were sent the DVD alone., Conclusions: Combining telephone-based PN with a mailed, tailored DVD increased CRC screening among low-income and minority patients who did not attend their screening colonoscopy appointments and has potential for wide dissemination., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Behavioral Medicine.)

A progressive neurological disorder was observed in a male neutered Weimaraner. Clinical signs included fecal incontinence, lethargy, moderate paraparesis, proprioceptive pelvic limb ataxia, falling, cognitive decline, incoordination, decreased interest in food, changes in posture, and episodes of trance-like behavior. Neurologic signs were first observed at approximately 4 years, 10 months of age and progressed slowly. Magnetic resonance imaging showed generalized brain atrophy with areas of white matter pathology. Humane euthanasia was elected at 6 years, 7 months of age due to increasing severity of the neurological signs. Autofluorescent intracellular granules were observed in the cerebral and cerebellar cortexes, optic nerve, and cardiac muscle of the affected dog. These abnormal inclusions in the cerebral cortex and cardiac muscle immunolabeled with antibodies to mitochondrial ATP synthase subunit c protein, like that observed in the neuronal ceroid lipofuscinosis group of lysosomal storage diseases. Immunolabeling also demonstrated pronounced neuroinflammation in brain tissues. The ultrastructural appearances of the disease-related inclusion bodies in the brain and optic nerve were quite variable. The ultrastructure and locations of many of the inclusions in the nervous tissues suggested that they were derived, at least in part, from the myelin surrounding axons. The storage bodies in the cardiac muscle were located in mitochondria-rich regions and consisted of parallel arrays of membrane-like components interspersed with electron-dense flocculent material. The disease was characterized by pronounced abnormalities in the myelin of the brain and optic nerve consisting of distinctive areas of ballooning between the layers of myelin. The whole genome sequence generated from the affected dog contained a homozygous G-to-A missense mutation in CNP , which encodes proteins with CNPase enzyme activity and a structural role in myelin. The mutation predicts a Thr42Met amino acid sequence substitution. Genotyping of archived Weimaraner DNA samples identified an additional G > A variant homozygote with a clinical history and brain lesions similar to those of the proband. Of 304 Weimaraners and over 4000 other dogs of various breeds, the proband and the other Weimaraner that exhibited similar signs were the only two that were homozygous for the CNP missense variant. CNPase immunolabeling was widespread in brain tissues from normal dogs but was undetectable in the same tissues from the proband. Based on the clinical history, fluorescence and electron-microscopy, immunohistochemistry, and molecular genetic findings, the late-onset Weimaraner disorder likely results from the missense mutation that results in CNPase deficiency, leading to myelin abnormalities, accumulation of lysosomal storage bodies, and brain atrophy. Similar disorders have been associated with different CNP variants in Dalmatians and in human subjects.

A 6-month-old cat of unknown ancestry presented for a neurologic evaluation due to progressive motor impairment. Complete physical and neurologic examinations suggested the disorder was likely to be hereditary, although the signs were not consistent with any previously described inherited disorders in cats. Due to the progression of disease signs including severely impaired motor function and cognitive decline, the cat was euthanized at approximately 10.5 months of age. Whole genome sequence analysis identified a homozygous missense variant c.2506G > A in MANBA that predicts a p.Gly836Arg alteration in the encoded lysosomal enzyme β -mannosidase. This variant was not present in the whole genome or whole exome sequences of any of the 424 cats represented in the 99 Lives Cat Genome dataset. β -Mannosidase enzyme activity was undetectable in brain tissue homogenates from the affected cat, whereas α-mannosidase enzyme activities were elevated compared to an unaffected cat. Postmortem examination of brain and retinal tissues revealed massive accumulations of vacuolar inclusions in most cells, similar to those reported in animals of other species with hereditary β -mannosidosis. Based on these findings, the cat likely suffered from β -mannosidosis due to the abolition of β -mannosidase activity associated with the p.Gly836Arg amino acid substitution. p.Gly836 is located in the C-terminal region of the protein and was not previously known to be involved in modulating enzyme activity. In addition to the vacuolar inclusions, some cells in the brain of the affected cat contained inclusions that exhibited lipofuscin-like autofluorescence. Electron microscopic examinations suggested these inclusions formed via an autophagy-like process., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Chronic pain disproportionately affects medically and psychosocially complex patients, many of whom are at high risk of hospitalisation. Pain prevalence among high-risk patients, however, is unknown, and pain is seldom a focus for improving high-risk patient outcomes. Our objective is to (1) evaluate pain frequency in a high-risk patient population and (2) identify intensive management (IM) programme features that patients and providers perceive as important for promoting patient-centred pain care within primary care (PC)-based IM., Design: Secondary observational analysis of quantitative and qualitative evaluation data from a multisite randomised PC-based IM programme for high-risk patients., Setting: Five integrated local Veterans Affairs (VA) healthcare systems within distinct VA administrative regions., Participants: Staff and high-risk PC patients in the VA., Intervention: A multisite randomised PC-based IM programme for high-risk patients., Outcome Measures: (a) Pain prevalence based on VA electronic administrative data and (b) transcripts of interviews with IM staff and patients that mentioned pain., Results: Most (70%, 2593/3723) high-risk patients had at least moderate pain. Over one-third (38%, 40/104) of the interviewees mentioned pain or pain care. There were 89 pain-related comments addressing IM impacts on pain care within the 40 interview transcripts. Patient-identified themes were that IM improved communication and responsiveness to pain. PC provider-identified themes were that IM improved workload and access to expertise. IM team member-identified themes were that IM improved pain care coordination, facilitated non-opioid pain management options and mitigated provider compassion fatigue. No negative IM impacts on pain care were mentioned., Conclusions: Pain is common among high-risk patients. Future IM evaluations should consider including a focus on pain and pain care, with attention to impacts on patients, PC providers and IM teams., Competing Interests: Competing interests: We have read and understand the BMJ policy on competing interest and all authors have completed the ICMJE COI disclosure form. To the best of our knowledge, all authors report no competing interests, financial or other, that exist, apart from one author who reported receiving personal fees from Behavioral Health Services, Inc, outside the submitted work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Colorectal cancer (CRC) screening is recommended for average-risk adults, yet many adults are not up-to-date with screening. One recommended CRC screening approach is the annual completion of a fecal immunochemical test (FIT). However, usually, fewer than half of mailed FIT tests are returned., Methods: To address barriers to FIT return, a video brochure was developed providing targeted CRC screening information and step-by-step FIT instructions as a component in a mailed FIT program. This pilot study occurred in 2021-2022 and partnered with a federally qualified health center in Appalachian Ohio to send a FIT to patients who were 50-64 years old, of average risk, and not up-to-date on CRC screening. Patients were randomly assigned to 1 of 3 groups that differed on materials sent with the FIT: usual care (manufacturer's instructions), a video brochure (video instructions, disposable gloves, disposable stool collection device), or an audio brochure (audio instructions, disposable gloves, disposable stool collection device)., Findings: Overall, 16 of 94 patients (17%) returned the FIT, and return was higher among those sent the video brochure (28%) compared to the other 2 groups (OR: 3.1; 95% CI: 1.02, 9.2; P = .046). Two patients had positive tests and were referred for colonoscopy. Patients sent the video brochure reported the content was important, relevant, and made them think about completing the FIT., Conclusions: Using a video brochure to provide understandable information in a mailed FIT kit is a promising strategy to improve CRC screening outreach programs in rural regions., (© 2023 The Authors. The Journal of Rural Health published by Wiley Periodicals LLC on behalf of National Rural Health Association.)

Process evaluation is essential to understanding and interpreting the results of randomized trials testing the effects of behavioral interventions. A process evaluation was conducted as part of a comparative effectiveness trial testing a mailed, tailored interactive digital video disc (DVD) with and without telephone-based patient navigation (PN) to promote breast, cervical and colorectal cancer screening among rural women who were not up-to-date (UTD) for at least one screening test. Data on receipt, uptake, and satisfaction with the interventions were collected via telephone interviews from 542 participants who received the tailored interactive DVD (n = 266) or the DVD plus telephone-based PN (n = 276). All participants reported receiving the DVD and 93.0% viewed it. The most viewed sections of the DVD were about colorectal, followed by breast, then cervical cancer screening. Most participants agreed the DVD was easy to understand, helpful, provided trustworthy information, and gave information needed to make a decision about screening. Most women in the DVD+PN group, 98.2% (n = 268), reported talking with the navigator. The most frequently discussed cancer screenings were colorectal (86.8%) and breast (71.3%); 57.5% discussed cervical cancer screening. The average combined length of PN encounters was 22.2 minutes with 21.7 additional minutes spent on coordinating activities. Barriers were similar across screening tests with the common ones related to the provider/health care system, lack of knowledge, forgetfulness/too much bother, and personal issues. This evaluation provided information about the implementation and delivery of behavioral interventions as well as challenges encountered that may impact trial results., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Behavioral Medicine.)

Purpose: To determine the prevalence of food insecurity (FI) among females with a history of breast cancer compared to females without cancer in the USA and the sociodemographic characteristics that may explain their FI., Methods: Using the 2019 National Health Interview (NHIS) survey that included the US Department of Agriculture's (USDA's) 10-item Household Food Security Survey Module, participants with high/moderate food security were considered food secure and low/very low food security were considered food insecure. Analyses accounted for complex survey design and included descriptive statistics, bivariate analyses, and multivariate regression analyses., Results: Eligible females (40+ years old) included 557 with a history of breast cancer and 9678 without a cancer history. FI was experienced by an estimated 4.4% of females with breast cancer, compared to 9.3% of females without cancer. Controlling for age, race/ethnicity, education level, general health status, and body mass index, the prevalence ratio between the two study groups was 0.50 (95% CI 0.33-0.78)., Conclusions: In this national sample, the prevalence of FI among females with a history breast cancer was lower than females without a history of cancer., Implications for Cancer Survivors: FI is low among breast cancer survivors, and routine FI screening among breast cancer survivors may not be warranted for all patients. Healthcare providers, however, should be aware of FI as a social determinant of health and consider it when there are known financial issues among cancer survivors., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Many healthcare systems seek to improve care for complex high-risk patients, but engaging such patients to actively participate in their healthcare can be challenging., Objective: To identify and describe types of patient engagement strategies reported as successfully deployed by providers/teams and experienced by patients in a Veterans Health Administration (VA) intensive primary care (IPC) pilot program., Methods: We conducted semi-structured qualitative telephone interviews with 29 VA IPC staff (e.g., physicians, nurses, psychologists) and 51 patients who had at least four IPC team encounters. Interviews were recorded, transcribed, and analyzed thematically using a combination a priori/inductive approach., Results: The engagement strategies successfully deployed by the IPC providers/teams could be considered either more "facilitative," i.e., facilitated by and dependent on staff actions, or more "self-sustaining," i.e., taught to patients, thus cultivating their ongoing patient self-care. Facilitative strategies revolved around enhancing patient access and coordination of care, trust-building, and addressing social determinants of health. Self-sustaining strategies were oriented around patient empowerment and education, caregiver and/or community support, and boundaries and responsibilities. When patients described their experiences with the "facilitative" strategies, many discussed positive proximal outcomes (e.g., increased access to healthcare providers). Self-sustaining strategies led to positive (self-reported) longer-term clinical outcomes, such as behavior change., Conclusion: We identified two categories of strategies for successfully engaging complex, high-risk patients: facilitative and self-sustaining. Intensive primary care program leaders may consider thoughtfully building "self-sustaining" engagement strategies into program development. Future research can confirm their effectiveness in improving health outcomes., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Genetic counseling and testing have an important role in the care of patients at elevated risk for breast cancer. However, conventional pre- and post-test genetic counseling is labor and time intensive, less accessible for patients living outside major urban centers, and impractical on a large scale. A patient-driven approach to genetic counseling and testing may increase access, improve patients' experiences, affect efficiency of clinical practice, and help meet workforce demand. The objective of this 2-arm randomized controlled trial is to determine the efficacy of Know Your Risk (KYR), a genetic counseling patient preference intervention., Methods: Females (n = 1000) at elevated risk (>20% lifetime) for breast cancer will be randomized to the KYR intervention or conventional genetic counseling. The study will provide comprehensive assessment of breast cancer risk by multigene panel testing and validated polygenic risk score. Primary outcome is adherence to National Comprehensive Cancer Network guidelines for a clinical encounter every 6-12 months and an annual mammogram (breast MRI if recommended) determined by medical record review. Secondary outcomes include adherence to other recommended cancer screening tests determined by medical record review and changes in breast cancer knowledge, perception of risk, post-test/counseling distress, and satisfaction with counseling by completion of three surveys during the study. Study aims will be evaluated for non-inferiority of the KYR intervention compared to conventional genetic counseling., Conclusion: If efficacious, the KYR intervention has the potential to improve patients' experience and may change how genetic counseling is delivered, inform best practices, and reduce workforce burden., Trial Registration: ClinicalTrials.govNCT05325151., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Appalachian regions of Kentucky and Ohio are hotspots for colorectal cancer (CRC) mortality in the USA. Screening reduces CRC incidence and mortality; however, screening uptake is needed, especially in these underserved geographic areas. Implementation science offers strategies to address this challenge. The aim of the current study was to conduct multi-site, transdisciplinary research to evaluate and improve CRC screening processes using implementation science strategies. The study consists of two phases (Planning and Implementation). In the Planning Phase, a multilevel assessment of 12 health centers (HC) (one HC from each of the 12 Appalachian counties) was conducted by interviewing key informants, creating community profiles, identifying HC and community champions, and performing HC data inventories. Two designated pilot HCs chose CRC evidence-based interventions to adapt and implement at each level (i.e., patient, provider, HC, and community) with evaluation relative to two matched control HCs. During the Implementation Phase, study staff will repeat the rollout process in HC and community settings in a randomized, staggered fashion in the remaining eight counties/HCs. Evaluation will include analyses of electronic health record data and provider and county surveys. Rural HCs have been reluctant to participate in research because of concerns about capacity; however, this project should demonstrate that research does not need to be burdensome and can adapt to local needs and HC abilities. If effective, this approach could be disseminated to HC and community partners throughout Appalachia to encourage the uptake of effective interventions to reduce the burden of CRC., (© Society of Behavioral Medicine 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

A 7-month-old Doberman Pinscher dog presented with progressive neurological signs and brain atrophy suggestive of a hereditary neurodegenerative disorder. The dog was euthanized due to the progression of disease signs. Microscopic examination of tissues collected at the time of euthanasia revealed massive accumulations of vacuolar inclusions in cells throughout the central nervous system, suggestive of a lysosomal storage disorder. A whole genome sequence generated with DNA from the affected dog contained a likely causal, homozygous missense variant in MAN2B1 that predicted an Asp104Gly amino acid substitution that was unique among whole genome sequences from over 4000 dogs. A lack of detectable α-mannosidase enzyme activity confirmed a diagnosis of a-mannosidosis. In addition to the vacuolar inclusions characteristic of α-mannosidosis, the dog exhibited accumulations of autofluorescent intracellular inclusions in some of the same tissues. The autofluorescence was similar to that which occurs in a group of lysosomal storage disorders called neuronal ceroid lipofuscinoses (NCLs). As in many of the NCLs, some of the storage bodies immunostained strongly for mitochondrial ATP synthase subunit c protein. This protein is not a substrate for α-mannosidase, so its accumulation and the development of storage body autofluorescence were likely due to a generalized impairment of lysosomal function secondary to the accumulation of α-mannosidase substrates. Thus, it appears that storage body autofluorescence and subunit c accumulation are not unique to the NCLs. Consistent with generalized lysosomal impairment, the affected dog exhibited accumulations of intracellular inclusions with varied and complex ultrastructural features characteristic of autophagolysosomes. Impaired autophagic flux may be a general feature of this class of disorders that contributes to disease pathology and could be a target for therapeutic intervention. In addition to storage body accumulation, glial activation indicative of neuroinflammation was observed in the brain and spinal cord of the proband.

Background: Routine human papillomavirus (HPV) vaccination is recommended for young adults, yet many young gay, bisexual, and other men who have sex with men (YGBMSM) remain unvaccinated. We report the efficacy of Outsmart HPV, a web-based HPV vaccination intervention for YGBMSM., Methods: From 2019 to 2021, we recruited YGBMSM in the United States who were ages 18-25 and unvaccinated against HPV (n = 1,227). Participants were randomized to receive either: (i) Outsmart HPV content online and monthly interactive text reminders (interactive group); (ii) Outsmart HPV content online and monthly unidirectional text reminders (unidirectional group); or (iii) standard information online about HPV vaccine (control group). Regression models compared study groups on HPV vaccination outcomes., Results: Overall, 33% of participants reported initiating the HPV vaccine series and 7% reported series completion. Initiation was more common among participants in the interactive group compared with the control group [odds ratio (OR) = 1.47, 98.3% confidence interval (CI): 1.03-2.11]. Completion was more common among participants in both the interactive group (OR = 3.70, 98.3% CI: 1.75-7.83) and unidirectional group (OR = 2.26, 98.3% CI: 1.02-5.00) compared with the control group. Participants who received Outsmart HPV content reported higher levels of satisfaction with online content compared with the control group., Conclusions: Outsmart HPV is an efficacious and acceptable HPV vaccination intervention for YGBMSM. Future efforts are needed to determine how to optimize the intervention and disseminate it to settings that provide services to YGBMSM., Impact: Outsmart HPV is a promising tool for increasing HPV vaccination among YGBMSM with the potential for wide dissemination., (©2023 American Association for Cancer Research.)

Objective: Insulin pump use is increasing among people with type 2 diabetes (T2D), albeit at a slower rate compared to people with type 1 diabetes (T1D). Factors associated with insulin pump initiation among people with T2D in the real-world are understudied., Methods: This retrospective, nested case-control study aimed to identify predictors of insulin pump initiation among people with T2D in the United States (US). Adults with T2D who were new to bolus insulin use were identified from the IBM MarketScan Commercial database (2015-2020). Candidate variables of pump initiation were entered into conditional logistic regression (CLR) and penalized CLR models., Results: Of the 32,104 eligible adults with T2D, 726 insulin pump initiators were identified and matched to 2,904 non-pump initiators using incidence density sampling. Consistent predictors of insulin pump initiation across the base case, sensitivity, and post hoc analyses included continuous glucose monitor (CGM) use, visiting an endocrinologist, acute metabolic complications, higher count of HbA1c tests, lower age, and fewer diabetes-related medication classes., Conclusions: Many of these predictors could represent a clinical indication for treatment intensification, greater patient engagement in diabetes management, or proactive management by healthcare providers. Improved understanding of predictors for pump initiation may lead to more targeted efforts to improve access and acceptance of insulin pumps among persons with T2D.

Importance: Women living in rural areas have lower rates of breast, cervical, and colorectal cancer screening compared with women living in urban settings., Objective: To assess the comparative effectiveness of (1) a mailed, tailored digital video disc (DVD) intervention; (2) a DVD intervention plus telephonic patient navigation (DVD/PN); and (3) usual care with simultaneously increased adherence to any breast, cervical, and colorectal cancer screening that was not up to date at baseline and to assess cost-effectiveness., Design, Setting, and Participants: This randomized clinical trial recruited and followed up women from rural Indiana and Ohio (community based) who were not up to date on any or all recommended cancer screenings. Participants were randomly assigned between November 28, 2016, and July 1, 2019, to 1 of 3 study groups (DVD, DVD/PN, or usual care). Statistical analyses were completed between August and December 2021 and between March and September 2022., Intervention: The DVD interactively assessed and provided messages for health beliefs, including risk of developing the targeted cancers and barriers, benefits, and self-efficacy for obtaining the needed screenings. Patient navigators counseled women on barriers to obtaining screenings. The intervention simultaneously supported obtaining screening for all or any tests outside of guidelines at baseline., Main Outcomes and Measures: Receipt of any or all needed cancer screenings from baseline through 12 months, including breast, cervical, and colorectal cancer, and cost-effectiveness of the intervention. Binary logistic regression was used to compare the randomized groups on being up to date for all and any screenings at 12 months., Results: The sample included 963 women aged 50 to 74 years (mean [SD] age, 58.6 [6.3] years). The DVD group had nearly twice the odds of those in the usual care group of obtaining all needed screenings (odds ratio [OR], 1.84; 95% CI, 1.02-3.43; P = .048), and the odds were nearly 6 times greater for DVD/PN vs usual care (OR, 5.69; 95% CI, 3.24-10.5; P < .001). The DVD/PN intervention (but not DVD alone) was significantly more effective than usual care (OR, 4.01; 95% CI, 2.60-6.28; P < .001) for promoting at least 1 (ie, any) of the needed screenings at 12 months. Cost-effectiveness per woman who was up to date was $14 462 in the DVD group and $10 638 in the DVD/PN group., Conclusions and Relevance: In this randomized clinical trial of rural women who were not up to date with at least 1 of the recommended cancer screenings (breast, cervical, or colorectal), an intervention designed to simultaneously increase adherence to any or all of the 3 cancer screening tests was more effective than usual care, available at relatively modest costs, and able to be remotely delivered, demonstrating great potential for implementing an evidence-based intervention in remote areas of the midwestern US., Trial Registration: ClinicalTrials.gov Identifier: NCT02795104.

Objective: To describe the development of a web-based, theory-guided narrative intervention that replaces conventional pre-test genetic counseling for women at elevated breast cancer risk., Methods: We used an iterative process that was guided by health behavior theory and feedback from multiple stakeholder groups including: 1) content input from genetic experts; 2) study team input; 3) review of video storyboards, video example, study logo, recruitment materials, post-test patient preference counseling survey, and additional study surveys; 4) video series development; and 5) intervention review and finalization of study-related materials., Results: The intervention is patient-centered providing convenience and an opportunity for an individual's preferences for post-test counseling delivery. The intervention's efficacy is being determined in a randomized controlled trial compared to conventional genetic counseling for adherence to recommended guidelines and changes in knowledge, perception of breast cancer risk, breast cancer-specific worry, and satisfaction with counseling., Conclusion: If efficacious, the intervention may improve the delivery of the genetic testing and counseling process, inform best practices, and reduce the genetic counseling workforce burden., Practice Implications: The developed intervention has the potential to improve the genetic testing and counseling experience for women at elevated risk for breast cancer, inform best practices, and reduce genetic counseling workforce burden., Competing Interests: Declaration of Competing Interest Mira Katz, Leigha Senter, Paul Reiter, Brent Emerson, Alysha Ennis, Kate Shane-Carson, Amber Aeilts, Hayley Cassingham, Patrick Schnell, Doreen Agnese, Amanda Toland, and Kevin Sweet declare no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

CLN2 neuronal ceroid lipofuscinosis is a rare hereditary neurodegenerative disorder characterized by deleterious sequence variants in TPP1 that result in reduced or abolished function of the lysosomal enzyme tripeptidyl peptidase 1 (TPP1). Children with this disorder experience progressive neurological decline and vision loss starting around 2-4 years of age. Ocular disease is characterized by progressive retinal degeneration and impaired retinal function culminating in total loss of vision. Similar retinal pathology occurs in a canine model of CLN2 disease with a null variant in TPP1. A study using the dog model was performed to evaluate the efficacy of ocular gene therapy to provide a continuous, long-term source of human TPP1 (hTPP1) to the retina, inhibit retinal degeneration and preserve retinal function. TPP1 -/- dogs received an intravitreal injection of 1 x 10 12 viral genomes of AAV2.CAG.hTPP1 in one eye and AAV2.CAG.GFP in the contralateral eye at 4 months of age. Ophthalmic exams, in vivo ocular imaging and electroretinography were repeated monthly to assess retinal structure and function. Retinal morphology, hTPP1 and GFP expression in the retina, optic nerve and lateral geniculate nucleus, and hTPP1 concentrations in the vitreous were evaluated after the dogs were euthanized at end stage neurological disease at approximately 10 months of age. Intravitreal administration of AAV2.CAG.hTPP1 resulted in stable, widespread expression of hTPP1 throughout the inner retina, prevented disease-related declines in retinal function and inhibited disease-related cell loss and storage body accumulation in the retina for at least 6 months. Uveitis occurred in eyes treated with the hTPP1 vector, but this did not prevent therapeutic efficacy. The severity of the uveitis was ameliorated with anti-inflammatory treatments. These results indicate that a single intravitreal injection of AAV2.CAG.hTPP1 is an effective treatment to inhibit ocular disease progression in canine CLN2 disease., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Rural women suffer disproportionately from breast, cervical, and colorectal cancer mortality compared to those in urban areas. Screening behaviors for these three cancers share many similar beliefs and barriers. Unfortunately, published interventions have not attempted to simultaneously bring women up to date with screening for three cancers (breast, cervical, and colorectal) even though multiple behavior change interventions are effective. The aim of this randomized controlled study was to compare the effectiveness of a mailed interactive and tailored DVD vs. DVD plus telephonic patient navigation (DVD + PN) vs. Usual Care (UC) to increase the percentage of rural women (aged 50-74) up to date for breast, cervical, and colorectal cancer screening., Methods: Nine hundred eighty-three participants needing one, two, or three cancer screening tests were consented and randomized to one of three groups. Prior to randomization, women were assessed for baseline characteristics including sociodemographics, health status, and cancer screening test beliefs. Screening status was assessed by medical record review., Results: At baseline, the average age of participants was 58.6 years. Nineteen percent of the sample was not up to date with screenings for all three cancers. Colorectal cancer had the highest percentage of women (69%) who were not up to date with screening followed by cervical (57%) and then breast cancer (41%). Sixty percent of women reported receiving a reminder for mammography; 30%, for cervical cancer screening; 15% for colonoscopy; and 6% for FOBT/FIT., Discussion: Increasing adherence to colorectal cancer screening may be the most urgent need among all screening tests. This clinical trial is registered at clinicaltrials.gov with identifier NCT02795104., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Paskett reports grants to the institution from Pfizer and Merck Foundation for work unrelated to the current project., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Knowledge, attitudes, and beliefs are important antecedents to HPV vaccination, yet remain suboptimal among young gay, bisexual, and other men who have sex with men (YGBMSM). We report the effects of a theoretically-informed, web-based HPV vaccination intervention on these cognitive outcomes. From 2019-2021, we recruited a national sample of YGBMSM ages 18-25 in the United States who were unvaccinated against HPV ( n  = 1,227). Participants received either standard HPV vaccination information online (control) or population-targeted, individually-tailored content online ( Outsmart HPV intervention). Mixed effects models determined if pre-post changes in cognitive outcomes differed between study groups. For five of seven knowledge items about HPV, there were larger pre-post increases among the intervention group than the control group in the percentage of participants who provided correct responses (all statistically significant at p  = .05 after Holm's correction). There were also larger pre-post improvements among the intervention group than the control group for most attitudes and beliefs examined, including response efficacy of HPV vaccine (pre-post increases in means: 0.57 vs. 0.38); self-efficacy for the HPV vaccination process (pre-post increases in means: 0.23 vs. 0.10); and intention to get HPV vaccine (pre-post increases in means: 0.70 vs. 0.28) (all statistically significant at p  = .05 after Holm's correction). Outsmart HPV is a promising tool for improving key cognitive antecedents to HPV vaccination among YGBMSM, supporting the use of theoretically-informed interventions to affect such outcomes. If efficacious in increasing HPV vaccine uptake in future analyses, this intervention could be utilized in clinical and other healthcare settings that provide services to YGBMSM.

This study examines the accuracy of the self-report of up-to-date cancer screening behaviors (Mammography, Papanicolaou (Pap)/Human Papillomavirus (HPV) tests, Fecal Occult Blood Test (FOBT)/Fecal Immunochemical Test (FIT), Colonoscopy) compared to medical record documentation prior to eligibility determination and enrollment in a randomized controlled trial of an intervention to increase cancer screening among women living in rural counties of Indiana and Ohio. Women (n = 1,641) completed surveys and returned a medical record release form from November 2016-June 2019. We compared self-report to medical records for up-to-date cancer screening behaviors to determine the validity of self-report. Logistic regression models identified variables associated with accurate reporting. Women were up-to-date for mammography (75 %), Pap/HPV test (54 %), colonoscopy (53 %), and FOBT/FIT (6 %) by medical record. Although 39.6 % of women reported being up-to-date for all three anatomic sites (breast, cervix, and colon), only 31.8 % were up to date by medical records. Correlates of accurate reporting of up-to-date cancer screening varied by screening test. Approximately-one-third of women in rural counties in the Midwest are up-to-date for all three anatomic sites and correlates of the accurate reporting of screening varied by test. Although most investigators use medical records to verify completion of cancer screening behaviors as the primary outcome of intervention trials, they do not usually use medical records for the routine verification of study eligibility. Study results suggest that future research should use medical record documentation of cancer screening behaviors to determine eligibility for trials evaluating interventions to increase cancer screening., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: EDP is the MPI of grants awarded to the institution from Merck Foundation, Pfizer and Genentech outside the scope of this work. The authors declare no conflict of interest. The funder had no role in the design of the study; in the collection, analyses, or interpretation of data, in the writing of the manuscript; or in the decision to publish the results., (© 2022 The Authors. Published by Elsevier Inc.)

Tissue fragility, skin hyperextensibility and joint hypermobility are defining characteristics of Ehlers-Danlos syndrome (EDS). Human EDS is subclassified into fourteen types including dermatosparactic EDS, characterized by extreme skin fragility and caused by biallelic ADAMTS2 mutations. We report two novel, ADAMTS2 variants in DNA from EDS-affected dogs. Separate whole-genome sequences from a Pit Bull Terrier and an Alapaha Blue Blood Bulldog each contained a rare, homozygous variant (11:2280117delC, CanFam3.1), predicted to produce a frameshift in the transcript from the first coding ADAMTS2 exon (c.10delC) and a severely truncated protein product, p.(Pro4ArgfsTer175). The clinical features of these dogs and 4 others with the same homozygous deletion included multifocal wounds, atrophic scars, joint hypermobility, narrowed palpebral fissures, skin hyperextensibility, and joint-associated swellings. Due to severe skin fragility, the owners of all 6 dogs elected euthanasia before the dogs reached 13 weeks of age. Cross sections of collagen fibrils in post-mortem dermal tissues from 2 of these dogs showed hieroglyphic-like figures similar to those from cases of severe dermatosparaxis in other species. The whole-genome sequence from an adult Catahoula Leopard Dog contained a homozygous ADAMTS2 missense mutation, [11:2491238G>A; p.(Arg966His)]. This dog exhibited multifocal wounds, atrophic scars, and joint hypermobility, but has survived for at least 9 years. This report expands the spectrum of clinical features of the canine dermatosparactic subtype of EDS and illustrates the potential utility of subclassifying canine EDS by the identity of gene harboring the causal variant.

Guideline-based mammography screening is essential to lowering breast cancer mortality, yet women residing in rural areas have lower rates of up to date (UTD) breast cancer screening compared to women in urban areas. We tested the comparative effectiveness of a tailored DVD, and the DVD plus patient navigation (PN) intervention vs. Usual Care (UC) for increasing the percentage of rural women (aged 50 to 74) UTD for breast cancer screening, as part of a larger study. Four hundred and two women who were not UTD for breast cancer screening, eligible, and between the ages of 50 to 74 were recruited from rural counties in Indiana and Ohio. Consented women were randomly assigned to one of three groups after baseline assessment of sociodemographic variables, health status, beliefs related to cancer screening tests, and history of receipt of guideline-based screening. The mean age of participants was 58.2 years with 97% reporting White race. After adjusting for covariates, 54% of women in the combined intervention (DVD + PN) had a mammogram within the 12-month window, over 5 times the rate of becoming UTD compared to UC (OR = 5.11; 95% CI = 2.57, 10.860; p < 0.001). Interactions of the intervention with other variables were not significant. Significant predictors of being UTD included: being in contemplation stage (intending to have a mammogram in the next 6 months), being UTD with other cancer screenings, having more disposable income and receiving a reminder for breast screening. Women who lived in areas with greater Area Deprivation Index scores (a measure of poverty) were less likely to become UTD with breast cancer screening. For rural women who were not UTD with mammography screening, the addition of PN to a tailored DVD significantly improved the uptake of mammography. Attention should be paid to certain groups of women most at risk for not receiving UTD breast screening to improve breast cancer outcomes in rural women.

A process evaluation was conducted as part of a comparative effectiveness trial of a mailed interactive educational DVD intervention to promote colorectal cancer screening among average-risk patients who did not attend a scheduled colonoscopy. Participants (n = 371) for the trial were randomized to (1) mailed DVD, (2) mailed DVD plus patient navigation, or (3) usual care. Participants (n = 243) randomized to the two DVD intervention arms were called 2 weeks after mailing materials to complete a process evaluation interview about the DVD (September 2017-February 2020). Forty-nine (20%) participants were not reached, and 194 (80%) participants watched the DVD and completed the interview. The process evaluation assessed whether (1) the DVD content was helpful, (2) any new information was learned by participants, (3) the appropriate amount of information was included in the DVD, (4) participants were engaged when watching the DVD, (5) the DVD content was relevant, (6) participants were satisfied with the DVD (7) participants would recommend the DVD to others, and (8) their opinion about colorectal cancer screening was changed by watching the DVD. Among participants who watched the DVD, 99% reported the screening information was very or somewhat helpful, 47% learned new information, 75% said the DVD included the right amount of information, they were engaged (M = 3.35 out of 4, SD = 0.49), 87% reported all or most information applied to them, they were satisfied (M = 3.42 out of 4, SD = 0.39) with DVD content, 99% would recommend the DVD to others, and 45% reported changing their opinion about screening. To understand the effects of interventions being tested in trials and to plan the dissemination of evidence-based interventions, process evaluation is critical to assess the dose received and acceptability of behavioral interventions.

A progressive neurological disorder was identified in purebred Dalmatian dogs. The disease is characterized by anxiety, pacing and circling, hypersensitivity, cognitive decline, sleep disturbance, loss of coordination, loss of control over urination and defecation, and visual impairment. Neurological signs first became apparent when the dogs were approximately 18 months of age and progressed slowly. Two affected littermates were euthanized at approximately 7 years, 5 months and 8 years, 2 months of age due to the severity of neurological impairment. The mother of the affected dogs and four other relatives exhibited milder, later-onset neurological signs. Pronounced accumulations of autofluorescent intracellular inclusions were found in cerebral cortex, cerebellum, optic nerve, and cardiac muscle of the affected dogs. These inclusions co-localized with immunolabeling of the lysosomal marker protein LAMP2 and bound antibodies to mitochondrial ATPase subunit c, indicating that the dogs suffered from a lysosomal storage disease with similarities to the neuronal ceroid lipofuscinoses. Ultrastructural analysis indicated that the storage bodies were surrounded by a single-layer membrane, but the storage granules were distinct from those reported for other lysosomal storage diseases. Whole genome sequences, generated with DNA from the two euthanized Dalmatians, both contained a rare, homozygous single-base deletion and reading-frame shift in CNP which encodes the enzyme CNPase (EC 3.1.4.37). The late-onset disease was exhibited by five of seven related Dalmatians that were heterozygous for the deletion allele and over 8 years of age, whereas none of 16 age-matched reference-allele homozygotes developed neurologic signs. No CNPase antigen could be detected with immunohistochemical labeling in tissues from the dogs with the earlier-onset disorder. Similar to the later-onset Dalmatians, autofluorescent storage granules were apparent in brain and cardiac tissue from transgenic mice that were nullizygous for Cnp. Based on the clinical signs, the histopathological, immunohistochemical, ultrastructural, and molecular-genetic findings, and the finding that nullizygous Cnp mice accumulate autofluorescent storage granules, we propose that the earlier-onset Dalmatian disorder is a novel lysosomal storage disease that results from a loss-of-function mutation in CNP and that shares features characteristic of the neuronal ceroid lipofuscinoses. That the later-onset disorder occurred only in dogs heterozygous for the CNP deletion variant suggests that this disorder is a result of the variant allele's presence., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Intensive primary care programs have had variable impacts on clinical outcomes, possibly due to a lack of consensus on appropriate patient-selection. The US Veterans Health Administration (VHA) piloted an intensive primary care program, known as Patient Aligned Care Team Intensive Management (PIM), in five medical centers. We sought to describe the PIM patient selection process used by PIM teams and to explore perspectives of PIM team members regarding how patient selection processes functioned in context., Methods: This study employs an exploratory sequential mixed-methods design. We analyzed qualitative interviews with 21 PIM team and facility leaders and electronic health record (EHR) data from 2,061 patients screened between July 2014 and September 2017 for PIM enrollment. Qualitative data were analyzed using a hybrid inductive/deductive approach. Quantitative data were analyzed using descriptive statistics., Results: Of 1,887 patients identified for PIM services using standardized criteria, over half were deemed inappropriate for PIM services, either because of not having an ambulatory care sensitive condition, living situation, or were already receiving recommended care. Qualitative analysis found that team members considered standardized criteria to be a useful starting point but too broad to be relied on exclusively. Additional data collection through chart review and communication with the current primary care team was needed to adequately assess patient complexity. Qualitative analysis further found that differences in conceptualizing program goals led to conflicting opinions of which patients should be enrolled in PIM., Conclusions: A combined approach that includes clinical judgment, case review, standardized criteria, and targeted program goals are all needed to support appropriate patient selection processes., (Published by Elsevier Inc.)

Golden Retriever dogs with a frameshift variant in CLN5 (c.934&#95;935delAG) suffer from a progressive neurodegenerative disorder analogous to the CLN5 form of neuronal ceroid lipofuscinosis (NCL). Five littermate puppies homozygous for the deletion allele were identified prior to the onset of disease signs. Studies were performed to characterize the onset and progression of the disease in these dogs. Neurological signs that included restlessness, unwillingness to cooperate with the handlers, and proprioceptive deficits first became apparent at approximately 12 months of age. The neurological signs progressed over time and by 21 to 23 months of age included general proprioceptive ataxia, menace response deficits, aggressive behaviors, cerebellar ataxia, intention tremors, decreased visual tracking, seizures, cognitive decline, and impaired prehension. Due to the severity of these signs, the dogs were euthanized between 21 and 23 months of age. Magnetic resonance imaging revealed pronounced progressive global brain atrophy with a more than sevenfold increase in the volume of the ventricular system between 9.5 and 22.5 months of age. Accompanying this atrophy were pronounced accumulations of autofluorescent inclusions throughout the brain and spinal cord. Ultrastructurally, the contents of these inclusions were found to consist primarily of membrane-like aggregates. Inclusions with similar fluorescence properties were present in cardiac muscle. Similar to other forms of NCL, the affected dogs had low plasma carnitine concentrations, suggesting impaired carnitine biosynthesis. These data on disease progression will be useful in future studies using the canine model for therapeutic intervention studies., (© 2022 The Authors. Developmental Neurobiology published by Wiley Periodicals LLC.)