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Oxidative stress plays a major role in diabetes. In vivo levels of membrane-bound radicals (MBRs) in a streptozotocin-induced diabetic mouse model were uniquely detected by combining molecular magnetic resonance imaging (mMRI) and immunotrapping techniques. An anti-DMPO (5,5-dimethyl-1-pyrroline N-oxide) antibody (Ab) covalently bound to an albumin (BSA)-Gd (gadolinium)-DTPA (diethylene triamine penta acetic acid)-biotin MRI contrast agent (anti-DMPO probe), and mMRI, were used to detect in vivo levels of DMPO-MBR adducts in kidneys, livers, and lungs of diabetic mice, after DMPO administration. Magnetic resonance signal intensities, which increase in the presence of a Gd-based molecular probe, were significantly higher within the livers, kidneys, and lungs of diabetic animals administered the anti-DMPO probe compared with controls. Fluorescence images validated the location of the anti-DMPO probe in excised tissues via conjugation of streptavidin-Cy3, which targeted the probe biotin moiety, and immunohistochemistry was used to validate the presence of DMPO adducts in diabetic mouse livers. This is the first report of noninvasively imaging in vivo levels of MBRs within any disease model. This method can be specifically applied toward diabetes models for in vivo assessment of free radical levels, providing an avenue to more fully understand the role of free radicals in diabetes. [ABSTRACT FROM AUTHOR]

The induction of macrophage death is considered a potential mechanism by which components secreted by Clostridium septicum are used to evade the innate immune response and cause tissue damage. This study aimed to determine the effects of partially purified fractions of extracellular proteins secreted by C. septicum on the death of mouse peritoneal macrophages. Elicited mouse peritoneal macrophages were incubated with partially purified fractions of proteins secreted by C. septicum into the culture medium. After incubation, the protein fraction with a molecular weight ≥100 kDa caused significant cell death in macrophages, altered cell morphology, increased the expression of markers of apoptosis and autophagy, and increased the expression (protein and mRNA) of IL-10 and TNFα. Our data suggest that the proteins secreted by C. septicum (MW, ≥100 kDa) induce cell death in macrophages by promoting autophagy-triggered apoptosis. This study may contribute to our understanding of the molecular mechanism of immune evasion by C. septicum at the infection site., 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 © 2024 Elsevier Ltd. All rights reserved.)

Background: Telemonitoring and telerehabilitation can support home-based pulmonary rehabilitation (PR) and benefit patients with lung diseases or COVID-19. This study aimed to (1) identify which telemonitoring and telerehabilitation interventions (e.g. videoconferencing) are used to provide telehealth care for people with chronic respiratory conditions or COVID-19, and (2) provide an overview of the effects of telemonitoring and telerehabilitation on exercise capacity, physical activity, health-related QoL (HRQoL), and healthcare use in patients with lung diseases or COVID-19., Methods: A search was performed in the electronic databases of Ovid MEDLINE, EMBASE, and Cinahl through 15 June 2021. Subject heading and keywords were used to reflect the concepts of telemonitoring, telerehabilitation, chronic lung diseases, and COVID-19. Studies that explored the effect of a telerehabilitation and/or telemonitoring intervention, in patients with a chronic lung disease such as asthma, chronic obstructive pulmonary diseases (COPD), or COVID-19, and reported the effect of the intervention in one or more of our outcomes of interest were included. Excluding criteria included evaluation of new technological components, teleconsultation or one-time patient assessment., Results: This scoping review included 44 publications reporting the effect of telemonitoring (25 studies), telerehabilitation (8 studies) or both (11 studies) on patients with COPD (35 studies), asthma (5 studies), COPD and asthma (1 study), and COVID-19 (2 studies). Patients who received telemonitoring and/or telerehabilitation had improvements in exercise capacity in 9 out of 11 (82%) articles, better HRQoL in 21 out of 25 (84%), and fewer health care use in 3 out of 3 (100%) articles compared to pre-intervention. Compared to controls, no statistically significant differences were found in the intervention groups' exercise capacity in 5 out 6 (83%) articles, physical activity in 3 out of 3 (100%) articles, HRQoL in 21 out of 25 (84%) articles, and healthcare use in 15 out of 20 (75%) articles. The main limitation of the study was the high variability between the characteristics of the studies, such as the number and age of the patients, the outcome measures, the duration of the intervention, the technological components involved, and the additional elements included in the interventions that may influence the generalization of the results., Conclusion: Telemonitoring and telerehabilitation interventions had a positive effect on patient outcomes and appeared to be as effective as standard care. Therefore, they are promising alternatives to support remote home-based rehabilitation in patients with chronic lung diseases or COVID-19., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Neisseria gonorrheae, the causative agent of genitourinary infections, has been associated with asymptomatic or recurrent infections and has the potential to form biofilms and induce inflammation and cell transformation. Herein, we aimed to use computational analysis to predict novel associations between chronic inflammation caused by gonorrhea infection and neoplastic transformation. Prioritization and gene enrichment strategies based on virulence and resistance genes utilizing essential genes from the DEG and PANTHER databases, respectively, were performed. Using the STRING database, protein‒protein interaction networks were constructed with 55 nodes of bacterial proteins and 72 nodes of proteins involved in the host immune response. MCODE and cytoHubba were used to identify 12 bacterial hub proteins (murA, murB, murC, murD, murE, purN, purL, thyA, uvrB, kdsB, lpxC, and ftsH) and 19 human hub proteins, of which TNF, STAT3 and AKT1 had high significance. The PPI networks are based on the connectivity degree (K), betweenness centrality (BC), and closeness centrality (CC) values. Hub genes are vital for cell survival and growth, and their significance as potential drug targets is discussed. This computational study provides a comprehensive understanding of inflammation and carcinogenesis pathways that are activated during gonorrhea infection., 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 © 2024 Elsevier Ltd. All rights reserved.)

Although the effectiveness of cardiac rehabilitation (CR) programs in secondary prevention is well-recognized, there is a lack of studies exploring the potential of mobile health to enhance educational interventions within CR. The objective is to assess the impact of a structured WhatsApp-assisted health educational intervention, in conjunction with the usual care, compared to the usual care alone among participants enrolled in a CR program. The trial will recruit 32 participants enrolled in a CR program, who will be randomly assigned to a structured WhatsApp-assisted health educational intervention plus usual care or usual care alone group. The intervention will span 4 weeks, with assessments at baseline, 4 weeks, and 3, 6, and 12 months. The primary outcome measure is the cardiovascular risk factors knowledge score. Secondary outcomes include physical activity levels, anxiety and depression, and quality of life. Expected results include improved knowledge of cardiovascular risk factors, increased physical activity levels, and better mental health outcomes in the intervention group. Additionally, an enhancement in the overall quality of life is anticipated. These findings are expected to underscore the value of integrating mHealth with traditional CR methods, potentially shaping future approaches in chronic disease management and prevention.

Background: This report involves the first publication describing a case of parietal abdominal pain due to lower limb length discrepancy., Case Presentation: A Caucasian male patient in his 50s was referred to our rehabilitation department with chronic abdominal pain that began in childhood. This chronic pain was associated with episodes of acute pain that were partially relieved by grade 3 analgesics. The patient was unable to sit for long periods, had recently lost his job, and was unable to participate in recreational activities with his children. Investigations revealed contracture and hypertrophy of the external oblique muscle and an limb length discrepancy of 3.8 cm (1.5 inches) in the left lower limb. The patient was effectively treated with a heel raise, physiotherapy, intramuscular injection of botulinum toxin, and lidocaine. The patient achieved the therapeutic goals of returning to work, and reducing analgesic use., Conclusions: Structural misbalances, as may be caused by lower leg discrepancy, may trigger muscular compensations and pain. Complete anamnesis and clinical examination must not be trivialized and may reveal previously ignored information leading to a proper diagnosis., (© 2024. The Author(s).)

The search for mechanism-based anti-inflammatory therapies is of fundamental importance to avoid undesired off-target effects. Phospholipase A 2 (PLA 2 ) activity is a potential molecular target for anti-inflammatory drugs because it fuels arachidonic acid needed to synthesize inflammation mediators, such as prostaglandins. Herein, we aim to investigate the molecular mechanism by which β-keto amyrin isolated from a methanolic extract of Cryptostegia grandiflora R. Br. Leaves can inhibit inflammation caused by Daboia russellii viper (DR) venom that mainly contains PLA 2 . We found that β-keto amyrin neutralizes DR venom-induced paw-edema in a mouse model. Molecular docking of PLA 2 with β-keto amyrin complex resulted in a higher binding energy score of -8.86 kcal/mol and an inhibition constant of 611.7 nM. Diclofenac had a binding energy of -7.04 kcal/mol and an IC50 value of 620 nM, which predicts a poorer binding interaction than β-keto amyrin. The higher conformational stability of β-keto amyrin interaction compared to diclofenac is confirmed by molecular dynamics simulation. β-keto amyrin isolated from C. grandiflora inhibits the PLA 2 activity contained in Daboia russellii viper venom. The anti-inflammatory property of β-keto amyrin is due to its direct binding into the active site of PLA 2 , thus inhibiting its enzyme activity., 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 © 2024 Elsevier Ltd. All rights reserved.)

Background: Chronic cough is a frequent reason for seeking consultation with primary care providers. The recent widespread adoption of virtual care offers a promising alternative that can be used to optimize the assessment and management of this condition. The objective of this review was to map and identify the strategies used to assess and/or manage chronic cough virtually, and to explore their impact on cough severity and patient satisfaction with virtual care., Methods: A scoping review was conducted in MEDLINE, EMBASE, and CINAHL in May 2023. Research questions were defined based on the Population, Concept, Context mnemonic, and literature search was conducted using a three-step approach. Study selection involved the steps of identification, screening, eligibility, and inclusion. A descriptive synthesis was performed, and quantitative variables were presented as absolute and relative frequencies., Results: A total of 4953 studies were identified and seven met the inclusion criteria. The following mHealth and telehealth strategies were identified: diagnostic website, specialized online clinic, online speech language therapy, and remote follow-up to assess the effectiveness of in-person interventions. Results indicated that these virtual strategies can be useful to assess chronic cough, treat, and track chronic cough symptoms. Overall, patients were satisfied with the approaches., Conclusion: Although literature is scarce, evidence suggests that virtual strategies for the assessment and management of chronic cough may be effective and are well-received by patients. However, further research is needed to identify the type and characteristics of virtual approaches leading to optimize and facilitate the care of patients with this condition. This will also help develop a strong body of evidence to support their incorporation into guidelines and clinical practice., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: The characteristics of optimal virtual pulmonary rehabilitation (PR) for individuals with post-COVID syndrome (PCS) have not been identified. This study aimed to assess the feasibility, safety, and satisfaction associated with a virtual PR program with the exercise component delivered through group or self-directed sessions., Methods: Adults with PCS-respiratory symptoms were randomly assigned to the video conference (PR VC ) or self-directed (PR SD ) group and completed an exercise program (aerobic, strengthening, and breathing exercises) three times/week for eight weeks. PR VC sessions were led by a physiotherapist via Zoom, whereas the PR SD group exercised individually following a pre-recorded video. Both groups received personalized exercise recommendations, education related to the condition, and a weekly follow up call. Satisfaction was assessed through a patient survey. Lung function, dyspnea, fatigue, sit-to-stand capacity, health-related quality of life, and participation were assessed pre- and post-PR., Results: Fourteen PCS individuals (49 ± 9 years, 86% females) completed 83% of the sessions. All participants were satisfied with information provided by the therapist and frequency of data submission, whereas most were satisfied with the frequency and duration of exercise sessions (88% in PR VC and 83% in PR SD ). A higher proportion of participants in the PR VC (88%) were satisfied with the level of difficulty of exercises compared with the PR SD (67%), and 84% of the sample reported a positive impact of the program on their health. No adverse events were reported. Significant changes in sit-to-stand capacity (p = 0.012, Cohen's r = 0.67) and questions related to fatigue (p = 0.027, Cohen's r = 0.58), neurocognitive (p = 0.045, Cohen's r = 0.53), and autonomic (p = 0.024, Cohen's r = 0.60) domains of the DePaul Symptom Questionnaire short-form were also found between groups., Conclusion: Virtual PR with exercises delivered via video conference or pre-recorded video were feasible, safe, and well-received by individuals with PCS., Trial Registration: NCT05003271 (first posted: 12/08/2021)., (© 2024. The Author(s).)

Introduction: The access and compliance of patients with interstitial lung diseases (ILDs) to exercise programs (EPs) remain challenges., Objectives: We assessed the dropout rate, intervention completion, compliance with data acquisition and submission, safety, and satisfaction of a home EP delivered via video conference (EP VC group) or self-directed (EP SD group) to patients with ILD. Pre- and post-intervention changes in patient outcomes (dyspnea, fatigue, exercise capacity, lung function, and quality of life) were secondarily explored., Material and Methods: Groups performed an eight-week virtual EP three times/week. Video conferences were led by a registered respiratory therapist, whereas self-directed exercises were completed following a pre-recorded video. Participants submitted spirometry, heart rate, and SpO 2 results weekly to the research team., Results: Fourteen patients with ILD were equally assigned to the EP VC and EP SD groups, but three from the EP SD group dropped out after the initial assessment (dropout rate of 42.8% in the EP SD group). Eleven patients (mean age of 67 ± 12 years) completed 96.5% of sessions. Compliance with data acquisition and submission was optimal (≥97.6% in both groups), and no adverse events were reported. Changes in overall fatigue severity were significantly different between groups ( p = 0.014, Cohen's r = 0.64)., Conclusions: The results suggest that a structured virtual EP delivered via video conference or pre-recorded video can be feasible, safe, and acceptable for patients with ILD.

This article reports on participants' experiences with long COVID-19 (LC) (symptoms, impact, healthcare use, and perceived needs) and satisfaction with a patient-oriented knowledge-sharing session organized by a multidisciplinary team of healthcare professionals, researchers, and a patient partner. Twenty-six participants completed a pre-session survey. On average, they were 21 months post-COVID-19 infection (SD 10.9); 81% of them were female, and 84% were 40+ years old. The main symptoms reported included fatigue (96%), cognitive problems (92%), and general pain or discomfort (40%). More than half of the participants reported that LC has had a significant impact on their health-related quality of life. Eighty-one percent of the participants reported seeking medical help for their LC symptoms and found the services provided by physical therapists, primary care providers, and acupuncturists to be helpful in managing their condition. Participants would like to have access to healthcare providers and clinics specializing in LC. They liked the session and found the information presented useful. This information helps to better understand the experiences of people living with LC and how to support their recovery.

Objective: This study aims to characterise respondents who have COVID-19 and long COVID syndrome (LCS), and describe their symptoms and healthcare utilisation., Design: Observational cross-sectional survey., Setting: The one-time online survey was available from June 2022 to November 2022 to capture the experience of residents in Manitoba, Canada., Participant: Individuals shared their experience with COVID-19 including their COVID-19 symptoms, symptoms suggestive of LCS and healthcare utilisation. We used descriptive statistics to characterise patients with COVID-19, describe symptoms suggestive of LCS and explore respondent health system use based on presenting symptoms., Results: There were 654 Manitobans who responded to our survey, 616 (94.2%) of whom had or provided care to someone who had COVID-19, and 334 (54.2%) reported symptoms lasting 3 or more months. On average, respondents reported having 10 symptoms suggestive of LCS, with the most common being extreme fatigue (79.6%), issues with concentration, thinking and memory (76.6%), shortness of breath with activity (65.3%) and headaches (64.1%). Half of the respondents (49.2%) did not seek healthcare for COVID-19 or LCS. Primary care was sought by 66.2% respondents with symptoms suggestive of LCS, 15.2% visited an emergency department and 32.0% obtained care from a specialist or therapist. 62.6% of respondents with symptoms suggestive of LCS reported reducing work, school or other activities which demonstrate its impact on physical function and health-related quality of life., Conclusion: Consistent with the literature, there are a variety of symptoms experienced among individuals with COVID-19 and LCS. Healthcare providers face challenge in providing care for patients with a wide range of symptoms unlikely to respond to a single intervention. These findings support the value of interdisciplinary COVID-19 clinics due to the complexity of the syndrome. This study confirms that data collected from the healthcare system do not provide a comprehensive reflection of LCS., Competing Interests: Competing interests: None declared., (© 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.)

Background: Studies exploring long COVID condition (LCC) in low- and middle-income countries are scarce. Further characterization of LCC patients experiencing activity limitations and their associated healthcare use is needed. This study aimed to describe LCC patients' characteristics, its impact on activities, and associated healthcare use in Latin America (LATAM)., Participants: Individuals who (cared for someone or) had COVID-19 and could read, write, and comprehend Spanish and lived in a LATAM country were invited to complete a virtual survey. Sociodemographic characteristics, COVID-19 and LCC symptoms, activity limitations, and healthcare use., Results: Data from 2,466 people from 16 countries in LATAM were analyzed (females = 65.9%; mean age of 39.5 ± 53.3 years). 1,178 (48%) of the respondents had LCC symptoms (≥3 months). These were more likely to have COVID-19 earlier in the pandemic, were older, had no COVID vaccines, had more comorbidities, needed supplementary oxygen, and reported significantly more COVID-19 symptoms during the infectious period. 33% of the respondents visited a primary care provider, 13% went to the emergency department, 5% were hospitalized, 21% visited a specialist, and 32% consulted ≥1 therapist for LCC symptoms mainly extreme fatigue, sleep difficulties, headaches, muscle or joint pain, and shortness of breath with activity. The most consulted therapists were respiratory therapists (15%) and psychologists (14%), followed by physical therapists (13%), occupational therapists (3%), and speech pathologists (1%). One-third of LCC respondents decreased their regular activities (e.g., work, school) and 8% needed help with activities of daily living (ADLs). LCC respondents who reduced their activities reported more difficulty sleeping, chest pain with activity, depression, and problems with concentration, thinking, and memory, while those who needed help with ADLs were more likely to have difficulty walking, and shortness of breath at rest. Approximately 60% of respondents who experienced activity limitations sought a specialist and 50% consulted therapists., Conclusions and Relevance: Results supported previous findings in terms of the LCC demographics, and provided insight into LCC impact on patients' activities and healthcare services used in LATAM. This information is valuable to inform service planning and resource allocation in alignment with the needs of this population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Angarita-Fonseca, Torres-Castro, Benavides-Cordoba, Chero, Morales-Satán, Hernández-López, Salazar-Pérez, Larrateguy and Sanchez-Ramirez.)

Case: A 65-year-old man with osteoarthritis of the hip developed a soft-tissue mass of the inferior gluteal region 3 years after metal-on-metal resurfacing hip arthroplasty. Clinical and imaging findings suggested an adverse local tissue reaction. Intraoperatively, nearly 1 liter of intra-articular fibrinous loose bodies (rice bodies) was removed, and histology showed features of an adaptive immune response. The patient had no evidence of an autoimmune disease or mycobacterial infection., Conclusion: To our knowledge, this is the first reported case of florid rice bodies associated with a metal-on-metal hip arthroplasty and adverse local tissue reaction., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/C69)., (Copyright © 2023 by The Journal of Bone and Joint Surgery, Incorporated.)

Plant breeders have indirectly selected for variation at circadian-associated loci in many of the world's major crops, when breeding to increase yield and improve crop performance. Using an eight-parent Multiparent Advanced Generation Inter-Cross (MAGIC) population, we investigated how variation in circadian clock-associated genes contributes to the regulation of heading date in UK and European winter wheat (Triticum aestivum) varieties. We identified homoeologues of EARLY FLOWERING 3 (ELF3) as candidates for the Earliness per se (Eps) D1 and B1 loci under field conditions. We then confirmed a single-nucleotide polymorphism within the coding region of TaELF3-B1 as a candidate polymorphism underlying the Eps-B1 locus. We found that a reported deletion at the Eps-D1 locus encompassing TaELF3-D1 is, instead, an allele that lies within an introgression region containing an inversion relative to the Chinese Spring D genome. Using Triticum turgidum cv. Kronos carrying loss-of-function alleles of TtELF3, we showed that ELF3 regulates heading, with loss of a single ELF3 homoeologue sufficient to alter heading date. These studies demonstrated that ELF3 forms part of the circadian oscillator; however, the loss of all homoeologues was required to affect circadian rhythms. Similarly, loss of functional LUX ARRHYTHMO (LUX) in T. aestivum, an orthologue of a protein partner of Arabidopsis (Arabidopsis thaliana) ELF3, severely disrupted circadian rhythms. ELF3 and LUX transcripts are not co-expressed at dusk, suggesting that the structure of the wheat circadian oscillator might differ from that of Arabidopsis. Our demonstration that alterations to ELF3 homoeologues can affect heading date separately from effects on the circadian oscillator suggests a role for ELF3 in cereal photoperiodic responses that could be selected for without pleiotropic deleterious alterations to circadian rhythms., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Human heparan sulfatase-2 (HSULF-2) is an oncoprotein overexpressed in the surface of all types of tumor cells and its activity plays a critical role in cancer survival and progression. Our previous studies have shown that bael fruit extract, containing marmesin and marmelosin, inhibits the HSULF-2 activity and kills breast tumor cells, but the mechanism of these processes remains fairly known mainly because the HSULF-2's 3D structure is partially known. Herein, we aimed at providing an in silico molecular mechanism of the inhibition of human HSULF-2 by phytochemicals from bael fruit extract. Pharmacokinetic parameters of the main phytochemicals contained in the bael fruit extract, sequence-based 3D structure of human HSULF-2, and the interaction of bael fruit's phytochemicals with the enzyme active site was modeled, evaluated, and verified. Docking studies revealed marmesin and marmelosin as potential inhibitors with binding score -8.5 and -7.7 Kcal/mol; these results were validated using molecular dynamics simulations, which exhibited higher stability of the protein-ligand complexes. Taking together, with our earlier in vitro data, our computational analyses suggest that marmesin and marmelosin interact at the active site of HSULF-2 providing a potential mechanism for its inhibition and consequent antitumor activity by phytochemicals contained in the bael fruit extract., Competing Interests: HC, RBS, RGA, DCR, and KSV have no conflict of interest to disclose., (Copyright © 2023 C. Hemakumar et al.)

Background: The long-term sequela of COVID-19 on young people is still unknown. This systematic review explored the effect of COVID-19 on lung imaging and function, cardiorespiratory symptoms, fatigue, exercise capacity and functional capacity in children and adolescents ≥ 3 months after infection., Methods: A systemic search was completed in the electronic databases of PubMed, Web of Science and Ovid MEDLINE on 27 May 2022. Data on the proportion of participants who had long-term effects were collected, and one-group meta-analysis were used to estimate the pooled prevalence of the outcomes studied., Results: 17 articles met the inclusion criteria, presented data on 124,568 children and adolescents. The pooled prevalence of abnormalities in lung imaging was 10% (95% CI 1-19, I 2 = 73%), abnormal pulmonary function was 24% (95% CI 4-43, I 2 = 90%), chest pain/tightness was 6% (95% CI 3-8, I 2 = 100%), heart rhythm disturbances/palpitations was 6% (95% CI 4-7, I 2 = 98%), dyspnea/breathing problems was 16% (95% CI 14-19, I 2 = 99%), and fatigue was 24% (95% CI 20-27, I 2 = 100%). Decreased exercise capacity and functional limitations were found in 20% (95% CI 4-37, I 2 = 88%) and 48% (95% CI 25-70, I 2 = 91%) of the participants studied, respectively., Conclusion: Children and adolescents may have persistent abnormalities in lung imaging and function, cardiorespiratory symptoms, fatigue, and decreased functional capacity between 3 to 12 months after infection. More research is needed to understand the long-term effect of COVID-19 on young people, and to clarify its causes and effective management.

Inhibition of Shaker K+ channel activity by external Na+ was previously reported in the melon (Cucumis melo L.) inwardly rectifying K+ channel MIRK and was hypothesized to contribute to salt tolerance. In this study, two inward Shaker K+ channels, CsKAT2 from cucumber (Cucumis sativus) and ClKAT2 from watermelon (Citrullus lanatus), were identified and characterized in Xenopus oocytes. Both channels were inwardly rectifying K+ channels with higher permeability to potassium than other monovalent cations and more active when external pH was acidic. Similarly to MIRK, their activity displayed an inhibition by external Na+, thus suggesting a common feature in Cucurbitaceae (Cucumis spp., Citrullus spp.). CsKAT2 and ClKAT2 are highly expressed in guard cells. After 24 h of plant treatment with 100 mM NaCl, the three KAT2-like genes were significantly downregulated in leaves and guard cells. Reciprocal chimeras were obtained between MIRK and Na+-insensitive AtKAT2 cDNAs. The chimera where the MIRK S5-P-S6 segment was replaced by that from AtKAT2 no longer showed Na+ sensitivity, while the inverse chimera gained Na+ sensitivity. These results provide evidence that the molecular basis of the channel blockage by Na+ is located in the S5-P-S6 region. Comparison of the electrostatic property in the S5-P-S6 region in AtKAT2 and MIRK revealed four key amino acid residues potentially governing Na+ sensitivity., (© The Author(s) 2021. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: People from lower and middle socioeconomic classes and vulnerable populations are among the worst affected by the COVID-19 pandemic, thus exacerbating disparities and the digital divide., Objective: To draw a portrait of e-services as a digital approach to support digital health literacy in vulnerable populations amid the COVID-19 infodemic, and identify the barriers and facilitators for their implementation., Methods: A scoping review was performed to gather published literature with a broad range of study designs and grey literature without exclusions based on country of publication. A search was created in Medline (Ovid) in March 2021 and translated to Medline, PsycINFO, Scopus and CINAHL with Full Text (EBSCOhost). The combined literature search generated 819 manuscripts. To be included, manuscripts had to be written in English, and present information on digital intervention(s) (e.g. social media) used to enable or increase digital health literacy among vulnerable populations during the COVID-19 pandemic (e.g. older adults, Indigenous people living on reserve)., Results: Five articles were included in the study. Various digital health literacy-enabling e-services have been implemented in different vulnerable populations. Identified e-services aimed to increase disease knowledge, digital health literacy and social media usage, help in coping with changes in routines and practices, decrease fear and anxiety, increase digital knowledge and skills, decrease health literacy barriers and increase technology acceptance in specific groups. Many facilitators of digital health literacy-enabling e-services implementation were identified in expectant mothers and their families, older adults and people with low-income. Barriers such as low literacy limited to no knowledge about the viruses, medium of contamination, treatment options played an important role in distracting and believing in misinformation and disinformation. Poor health literacy was the only barrier found, which may hinder the understanding of individual health needs, illness processes and treatments for people with HIV/AIDS., Conclusions: The literature on the topic is scarce, sparse and immature. We did not find any literature on digital health literacy in Indigenous people, though we targeted this vulnerable population. Although only a few papers were included, two types of health conditions were covered by the literature on digital health literacy-enabling e-services, namely chronic conditions and conditions that are new to the patients. Digital health literacy can help improve prevention and adherence to a healthy lifestyle, improve capacity building and enable users to take the best advantage of the options available, thus strengthening the patient's involvement in health decisions and empowerment, and finally improving health outcomes. Therefore, there is an urgent need to pursue research on digital health literacy and develop digital platforms to help solve current and future COVID-19-related health needs., (© The Author(s) 2022.)

Background: the effect of pulmonary rehabilitation (PR) services, beyond research contexts, on patients with lung diseases other than COPD requires further study., Objectives: to (i) assess the impact of a publicly funded PR on patients' exercise capacity, self-efficacy, and health-related quality of life (HRQoL), and (ii) explore whether the effects vary across lung diseases., Methods: this retrospective pre-post study analyzed data from the Winnipeg Regional Health Authority PR program between 2016 and 2019., Results: 682 patients completed the full PR program. Pooled analyses found significant improvements in the patients' exercise capacity (six-minute walk test (6MWT) (13.6%), fatigue (10.3%), and dyspnea (6.4%)), Self-Efficacy for Managing Chronic Disease 6-Item Scale (SEMCD6) (11.6%), and HRQoL (Clinical COPD Questionnaire (CCQ) (18.5%) and St George's Respiratory Questionnaire (SGRQ) (10.9%)). The analyses conducted on sub-groups of patients with chronic obstructive pulmonary disease (COPD), asthma, bronchiectasis, interstitial lung diseases (ILDs), other restrictive lung diseases (e.g., obesity, pleural effusion, etc.), lung cancer, and pulmonary hypertension (PH) indicated that, except for patients with PH, all the patients improved in the 6MWT. Fatigue decreased in patients with COPD, ILDs, and other restrictive lung diseases. Dyspnea decreased in patients with COPD, asthma, and lung cancer. SEMCD6 scores increased in COPD, ILDs and PH patients. CCQ scores decreased in all lung diseases, except lung cancer and PH. SGRQ scores only decreased in patients with COPD., Conclusion: PR services had a significant impact on patients with different lung diseases. Therefore, publicly funded PR should be available as a critical component in the management of patients with these diseases.

Importance: Cough is a common symptom in idiopathic interstitial lung diseases (ILDs), there is little information of its management in primary care. The objective of this study was to explore the frequency of cough-related consultations and the medications prescribed to patients with ILDs in primary care., Methods: This retrospective cohort study used electronic medical records (EMR) from Manitoba primary care providers participating in the Manitoba Primary Care Research Network repository (2014-2019). Cough-related consults and the subsequent medications prescribed to patients with ILDs were identified in the EMR., Results: 295 patients with ILDs were identified, 73 (25%) of them had 141 cough-related consultations (mean 1.9, SD 1.3) during the period studied. In 50 (35%) of the consultations, patients were prescribed one or more of the following: inhaled bronchodilators (34%), nasal corticoids (18%), codeine/opiates (18%), antibiotics (14%), inhaled corticoids (14%), proton pump inhibitors (8%), cough preparations (6%), antihistamines (4%), and oral corticoids (2%). 13 (26%) subsequent cough-related consultations were identified within 6 months, mainly among patients who were prescribed cough preparations, nasal corticoids, antihistamines, and antibiotics., Conclusion: One-quarter of patients with ILDs consulted primary care due to cough, and about a third of them received a prescription to address potentially underlying causes of cough. Although further studies are required to explore the effect of the medications prescribed, recurrent cough consultations suggested that cough preparations, nasal corticoids, and antihistamines are among the least effective treatments. More research is needed to understand the causes and optimal treatment of cough in patients with ILDs.

Background: Student-run health initiatives in the community setting have been utilized to provide practical experience for undergraduate students to develop professional competencies, gain exposure to diverse populations, and to engage in activities of social accountability. There is much literature on student-run health initiatives; however, there is no consensus on a definition of this concept or a comprehensive synthesis of the literature that describes student-run health initiatives offered by students in pre-licensure healthcare education programs., Purpose: To provide a concept analysis of, and propose a definition for, student-run health initiatives that provide community-based services for students during pre-licensure health discipline education., Methods: A systematic literature search and review process was used to identify and synthesize peer-reviewed articles from 7 academic databases covering a range of pre-licensure health disciplines and education. Walker and Avant's framework for concept analysis was used to guide exploration of attributes, antecedents and consequences of student-run initiatives, and to inform development of a definition for this concept., Results: The review yielded 222 articles for data extraction and represented 17 distinct pre-licensure health disciplines, 18 health-related disciplines, and a range of other baccalaureate and graduate programs. Our analysis revealed 16 definitions, 5 attributes, 6 antecedents, and consequences identified for student-run health initiatives. Attributes were Provision of Service, Service is Free, Target Clientele, Volunteerism, and Student Governance. Antecedents included Purpose/Rationale, Affiliation with Academic Unit, Location and Partnerships, Funding and Resources, Professional Oversight, and Preparation for Student Role. Consequences were improved access to services and outcomes for clients; competency development, personal gains and interprofessional learning for students; and positive outcomes for broader systems, such as decrease of service utilization and cost/benefit., Conclusions: There was no clear conceptual definition for student-run health initiatives, but many defining characteristics and well-described exemplars in the literature. Given the variations in purpose and scope of these initiatives, particularly to distinguish degree of students' roles in operations and the involvement of academic institutions, we propose 3 distinct conceptual definitions: student-run, student-led, and student-infused health initiatives.

Objective: To explore whether participation in a series of cardiology continuing medical education (CME) activities affects primary care providers' (PCPs') lipid management for their patients., Design: This retrospective cohort study used a database of participation in cardiology CME activities (2011 to 2017) linked to electronic medical records. Statistical analyses were completed using logistic regression with generalized estimating equations., Setting: Manitoba., Participants: Patients receiving care from 225 PCPs participating in the Manitoba Primary Care Research Network., Main Outcome Measures: Recommended lipid management was defined as prescription of statins (yes or no) among patients diagnosed with cardiovascular disease (CVD), patients diagnosed with diabetes mellitus (DM; 40 years or older), and patients diagnosed with chronic kidney disease (CKD; 50 years and older) in 2017. Treatment was identified using the ATC (Anatomical Therapeutic Chemical) system (ATC code C10AA or C10B)., Results: After adjusting for relevant confounders, the odds of prescribing statins to patients with CVD, DM, or CKD among PCPs who did not participate in the cardiology CME activities were 50%, 55%, and 67% lower, respectively, than among PCPs who participated in 2 or more activities. The odds of prescribing statins to patients with CVD and DM among PCPs who participated in only 1 cardiology CME activity were also 67% and 63% lower, respectively, than among PCPs who participated in 2 or more activities., Conclusion: Results suggested that PCPs who participated in 2 or more cardiology CME activities were more likely to prescribe recommended lipid management (statins) for adults with CVD, DM, or CKD., (Copyright © 2022 the College of Family Physicians of Canada.)

A lot of diseases are characterized by an increased inflammatory response with an exacerbated production of free radicals. The anti-inflammatory effect of different compounds with antioxidant capacity, as polyphenols present in grape is well known. Therefore, the objective is to evaluate the anti-oxidant and anti-inflammatory activity of waste product of wine production.Six different non-toxic-marc-polar extracts from Malbec and Syrah grape varieties were obtained, their total phenol and flavonoid content were evaluated, and their antioxidant and anti-inflammatory activity were determined.High content of total phenols and flavonoids were found mainly in extracts obtained from Syrah (80.51 ± 16.63 g equivalent to gallic acid/100 g and 25.47 ± 3.33 g equivalent to quercetin/100 g). In addition, they had a high antioxidant effect (above 88.5% of ABTS inhibition by Syrah extracts). Finally, all extracts decreased the nitric oxide (NO) production, but this was more accented when extract from Syrah obtained by infusion was used, which decreased NO levels to baseline (4.46 µM).Taking together, our results show the potential pharmaceutical use of waste product of wine making to prevent or to treat diseases which inflammatory response is exacerbated.

Background: The long-term impact of COVID-19 is still unknown. This study aimed to explore post COVID-19 effects on patients chest computed tomography (CT), lung function, respiratory symptoms, fatigue, functional capacity, health-related quality of life (HRQoL), and the ability to return to work beyond 3 months post infection., Methods: A systematic search was performed on PubMed, Web of Science, and Ovid MEDLINE on 22 May 2021, to identify studies that reported persistent effects of COVID-19 beyond 3 months follow-up. Data on the proportion of patients who had the outcome were collected and analyzed using a one-group meta-analysis., Results: Data were extracted from 24 articles that presented information on a total of 5323 adults, post-infection, between 3 to 6 months after symptom onset or hospital discharge. The pooled prevalence of CT abnormalities was 59% (95% CI 44-73, I 2 = 96%), abnormal lung function was 39% (95% CI 24-55, I 2 = 94%), fatigue was 38% (95% CI 27-49, I 2 = 98%), dyspnea was 32% (95% CI 24-40, I 2 = 98%), chest paint/tightness was 16% (95% CI 12-21, I 2 = 94%), and cough was 13%, (95% CI 9-17, I 2 = 94%). Decreased functional capacity and HRQoL were found in 36% (95% CI 22-49, I 2 = 97%) and 52% (95% CI 33-71, I 2 = 94%), respectively. On average, 8 out of 10 of the patients had returned to work or reported no work impairment., Conclusion: Post-COVID-19 patients may experience persistent respiratory symptoms, fatigue, decreased functional capacity and decreased quality of life up to 6 months after infection. Further studies are needed to establish the extent to which post-COVID-19 effects continue beyond 6 months, how they interact with each other, and to clarify their causes and their effective management.

Human health is dependent on a plentiful and nutritious supply of food, primarily derived from crop plants. Rhythmic supply of light as a result of the day and night cycle led to the evolution of circadian clocks that modulate most plant physiology, photosynthesis, metabolism, and development. To regulate crop traits and adaptation, breeders have indirectly selected for variation at circadian genes. The pervasive impact of the circadian system on crops suggests that future food production might be improved by modifying circadian rhythms, engineering the timing of transgene expression, and applying agricultural treatments at the most effective time of day. We describe the applied research required to take advantage of circadian biology in agriculture to increase production and reduce inputs., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: Coronavirus disease has provoked much discussion since its first appearance. Despite it being widely studied all over the world, little is known about the impact of the disease on functional ability related to performing activities of daily living (ADL) in patients post COVID-19 infection., Objectives: To understand the impact of COVID-19 on ADL performance of adult patients and to describe the common scales used to assess performance of ADL on patients post-COVID-19., Methods: A systematic review was conducted. We included studies that applied a physical capacity test in COVID-19 patients, post-infection. Two independent reviewers analyzed the studies, extracted the data, and assessed the quality of the evidence., Results: A total of 1,228 studies were included, after removing duplicates, 1,005 abstracts were screened and of those 983 were excluded. A final number of nine studies which met the eligibility criteria were included. The findings revealed worsening of physical function and ADL performance in all patients post COVID-19 infection., Conclusion: All included studies found a reduction of ADL beyond the test or scale used, revealing a vital worsening of functional ability in ADL performance and consequently loss of independence in COVID-19 patients after the acute phase of infection. Functional ability status previous to COVID-19 is crucial for predicting the severity of the disease and mortality. Barthel Index and ADL score were the most used assessment tools across subjects with different intrinsic capacity and context levels., Competing Interests: The authors declare that they have no competing interests., (© 2021 Pizarro-Pennarolli et al.)

Background: An outbreak of Corona Virus Disease 2019 (COVID-19) has spread rapidly reaching over 3 million of confirmed cases worldwide. The association of respiratory diseases and smoking, both highly prevalent globally, with COVID-19 severity has not been elucidated. Given the gap in the evidence and the growing prevalence of COVID-19, the objective of this study was to explore the association of underlying respiratory diseases and smoking with severe outcomes in patients with COVID-19 infection., Methods: A systematic search was performed to identify studies reporting prevalence of respiratory diseases and/or smoking in relation with disease severity in patients with confirm COVID-19, published between January 1 to April 15, 2020 in English language. Pooled odds-ratio (OR) and 95% confidence intervals (95% CI) were calculated., Findings: Twenty two studies met the inclusion criteria. All the studies presented data of 13,184 COVID-19 patients (55% males). Patients with severe outcomes were older and a larger percentage were males compared with the non-severe. Pooled analysis showed that prevalence of respiratory diseases (OR 4.21; 95% CI, 2.9-6.0) and smoking (current smoking OR 1.98; 95% CI, 1.16-3.39 and former smoking OR 3.46; 95% CI, 2.46-4.85) were significantly associated with severe COVID-19 outcomes., Interpretation: Results suggested that underlying respiratory diseases, specifically COPD, and smoking were associated with severe COVID-19 outcomes. These findings may support the planning of preventive interventions and could contribute to improvements in the assessment and management of patient risk factors in clinical practice, leading to the mitigation of severe outcomes in patients with COVID-19 infection., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: A persistent issue in cancer drug development is the discordance between robust antitumor drug activity observed in laboratory models and the limited benefit frequently observed when patients are treated with the same agents in clinical trials. Difficulties in accurately modeling the complexities of human tumors may underlie this problem. To address this issue, we developed Comparative In Vivo Oncology (CIVO), which enables in situ investigation of multiple microdosed drugs simultaneously in a patient's tumor. This study was designed to test CIVO's safety and feasibility in patients with soft tissue sarcoma (STS)., Patients and Methods: We conducted a single arm, prospective, 13-patient pilot study. Patients scheduled for incisional biopsy or tumor resection were CIVO-injected 1 to 3 days prior to surgery. Saline or microdoses of anticancer agents were percutaneously injected into the tumor in a columnar fashion through each of eight needles. Following excision, drug responses were evaluated in the injected tissue., Results: The primary objective was met, establishing CIVO's feasibility and safety. Device-related adverse events were limited to transient grade 1 nonserious events. In addition, biomarker evaluation of localized tumor response to CIVO microinjected drugs by IHC or with NanoString GeoMx Digital Spatial Profiler demonstrated consistency with known mechanisms of action of each drug, impact on the tumor microenvironment, and historic clinical activity., Conclusions: These results are an advance toward use of CIVO as a translational research tool for early evaluation of investigational agents and drug combinations in a novel approach to phase 0 trials. See related commentary by Sleijfer and Lolkema, p. 3897 ., (©2020 American Association for Cancer Research.)

Significance: Pulmonary neurophilic inflammation (PNI) is the homing and activation of neutrophil with damage to the microvasculature. This process is involved in pulmonary damage in patients exposed to airborne pollutants (exogenous stressors) and also to systemic inflammation/oxidative stress (endogenous stressors) associated with noncommunicable diseases (NCDs). Recent Advances: PNI is an important trigger of the early onset and progression of NCD in susceptible patients exposed to airborne pollutants. Irritation of the lung microvasculature by exogenous and endogenous stressors causes PNI. Circulating endogenous stressors in NCD can cause PNI. Critical Issues: Air pollution-triggered PNI causes increased circulating endogenous stressors that can trigger NCD in susceptible patients. Systemic inflammation/oxidative stress associated with NCD can cause PNI. Inflammation/end-oxidation products of macromolecules are also potential biomarkers and therapeutic targets for NCD-triggered PNI- and PNI-triggered NCD. Future Directions: Understanding the molecular mechanism of PNI triggered by exogenous or endogenous stressors will help explain the early onset of NCD in susceptible patients exposed to air pollution. It can also help undercover biomarkers and mechanism-based therapeutic targets in air pollutant-triggered PNI, PNI-triggered NCD, and NCD-triggered PNI.

Follicular dendritic cell sarcoma (FDCS) is a rare and unusual cancer that arises from sustentacular cells of the lymph node that present antigen to B cells, rather than lymphocytes themselves. While surgery for primary disease is still paramount in primary management, for unresectable, recurrent and metastatic tumours, FDCS is frequently treated with anthracycline-based lymphoma chemotherapy regimens. In recent years, it is clear that Programmed Cell Death 1 (PD1)-directed immune checkpoint inhibitors (ICIs) are active in Hodgkin lymphoma, but significantly less active in non-Hodgkin's lymphoma. These data raised the question of whether FDCS respond to ICI therapy. We present two patients with FDCS who were treated with nivolumab and ipilimumab with evidence of tumour response. These cases also highlight the difficulty in arriving at a proper diagnosis, emphasising the need for expert review of pathology to optimise treatment for these and other patients with sarcoma., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Cancer-associated fibroblasts (CAFs) are a key component of the tumour microenvironment with diverse functions, including matrix deposition and remodelling, extensive reciprocal signalling interactions with cancer cells and crosstalk with infiltrating leukocytes. As such, they are a potential target for optimizing therapeutic strategies against cancer. However, many challenges are present in ongoing attempts to modulate CAFs for therapeutic benefit. These include limitations in our understanding of the origin of CAFs and heterogeneity in CAF function, with it being desirable to retain some antitumorigenic functions. On the basis of a meeting of experts in the field of CAF biology, we summarize in this Consensus Statement our current knowledge and present a framework for advancing our understanding of this critical cell type within the tumour microenvironment.

A chronic-positive energetic balance has been directly correlated with infertility in men, but the involved mechanisms remain unknown. Herein we investigated weather in a mouse model a chronic feeding with a diet supplemented with chicken fat affects sperm head morphology. To accomplish this, we fed mice for 16 weeks with either control food (low-fat diet, LFD) or control food supplemented with 22% chicken fat (high-fat diet, HFD). At the end of the feeding regimen, we measured: redox and inflammatory changes, cholesterol accumulation in testis and analyzed testicular morphological structure and ultra-structure and liver morphology. We found that the mice fed HFD resembled some features of the human metabolic syndrome, including systemic oxidative stress and inflammation, this group showed an increment in the following parameters; central adiposity (adiposity index: 1.07 ± 0.10 vs 2.26 ± 0.17), dyslipidemia (total cholesterol: 153.3 ± 2.6 vs 175.1 ± 8.08 mg/dL), insulin resistance (indirect Insulin resistance index, TG/HDL-c: 2.94 ± 0.33 vs 3.68 ± 0.15) and fatty liver. Increased cholesterol content measured by filipin was found in the testicles from HFD (fluorescence intensity increase to 50%), as well as an alteration of spermiogenesis. Most remarkably, a disorganized manchette-perinuclear ring complex and an altered morphology of the sperm head were observed in the spermatozoa of HFD-fed mice. These results add new information to our understanding about the mechanisms by which systemic oxidative stress and inflammation may influence sperm-head morphology and indirectly male fertility., (© 2019 Published by Elsevier Ltd.)

Chicken fat and fructose are added into food-processing to reduce costs and enhance acceptability; however, these additives turn food into unhealthy and hypercaloric meals. Herein we have hypothesized that chronic feeding with chicken fat and fructose, together or by separate, can cause pulmonary redox and inflammatory changes. These changes are particularly related to neutrophils and myeloperoxidase, with consequent changes in the organ histophysiology. To test this hypothesis, we fed mice for 16 weeks with either control food (low-fat diet, LFD) or control food supplemented with 22% chicken fat and with or without 10% fructose in the drinking water. At the end of the feeding regimen, we measured redox and inflammatory changes in the lung with particular emphasis on neutrophil accumulation/activation and molecular-histological markers of fibrosis. Our results suggest that a diet supplemented with chicken fat and fructose causes additive effects on pulmonary oxidative stress, inflammation, and a pro-fibrotic status. Neutrophilic inflammation may play a critical role in pulmonary pathology associated with metabolic syndrome.

Immuno-spin trapping detection of DNA radicals with the nitrone spin trap 5,5-dimethyl-1-pyrrloine N-oxide (DMPO) has made important contributions towards the understanding of DNA radicalization and genotoxicity at sites of inflammation. At sites of inflammation, one-electron oxidants and chloramines decay induce oxidation of genomic DNA, genotoxicity and cell transformation. Radicalization of DNA can result in either single- or double-strand breaks, or end-oxidation products at the sugar or bases. If not repaired, these modifications can lead to mutations and cell transformation. If trapped with DMPO, DNA-centered radical decay and subsequent formation of end-oxidation products are blocked. Herein we discuss recent literature regarding the use of immuno-spin trapping with DMPO to study DNA-centered radicals and their involvement in genotoxicity. This technique has shown the critical role of DNA radicalization in 8-oxo-dG formation and DNA strand breaks in isolated DNA, cells and in whole animals. Combination of technologies, including immuno-spin trapping and powerful chromatographic and sequencing techniques are needed to move forward the field towards the detection of specific genes that are susceptible to oxidative damage in cells located at sites of inflammation. This is important in order to provide novel information about genotoxicity mechanisms, as well as therapeutic possibilities of DMPO or its derivatives for preventing DNA-centered radical-mediated carcinogenesis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: The care of patients with diabetes mellitus (DM), compiled in the 2008 Canadian Diabetes Association clinical practice guidelines and in recommendations from the Choosing Wisely Canada program, is informed by a large body of evidence. This study sought to assess to what extent primary care providers (PCPs) incorporate recommended statin and sulfonylureas treatment in their care of patients with DM, and to identify the association between use of recommended care and PCP characteristics., Methods: This retrospective cohort study (2007-2017) used electronic medical records of 21,149 patients with DM receiving care from 240 PCPs participating in the Manitoba Primary Care Research Network., Results: PCPs prescribed statins to patients newly diagnosed with DM who were ≥40 years of age 41% of the time, with 45% of the prescriptions occurring ≤180 days after a new diagnosis (early treatment). PCPs least likely to prescribe recommended statin treatment had higher odds of being older (adjusted odds ratio [aOR], 1.05; 95% confidence interval [CI], 1.01 to 1.09) and fee-for-service funded (aOR, 4.36; 95% CI, 1.47 to 12.91). In addition, older PCPs (aOR, 1.06; 95% CI, 1.02 to 1.10) and women (aOR, 2.42; 95% CI, 1.11 to 5.28) were less likely to prescribe statin treatment early. Seventy-four percent of PCPs prescribed sulfonylureas to adults ≥65 years of age. No PCP characteristics were associated with prescription of sulfonylureas in the lower implementation quartile in the fully adjusted model., Conclusions: Results suggest that PCPs' practice does not always align with current evidence-based clinical guidelines or Choosing Wisely Canada recommendations for patients with DM. Some PCP's characteristics were associated with lower implementation of recommended evidence-based care. This information can help guide future targeted medical education., (Copyright © 2019 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Objectives: To examine injury-related health services use, defined as hospital admissions and emergency department (ED) visits, as well as mortality among Métis people in Alberta, and to compare those results with the entire Alberta population., Methods: This population-based descriptive epidemiological research used administrative data maintained by the Alberta Ministry of Health (AH), for the year 2013. Hospital morbidity data and Alberta Vital Statistics registry were extracted and included a unique personal number to identify individuals across multiple records. To identify injury and mortality cases among the Métis people in Alberta, administrative databases were linked to the Métis Nation of Alberta (MNA) Identification Registry. Age-standardized rates of injury-related health services usage and mortality were calculated and compared between Métis people and the entire Alberta population., Results: Age-standardized incidence rates (ASIRs) of all causes combined of injury-related visits to the ED and hospital admissions were 35% (p < 0.01) and 26% (p = 0.05) higher among Métis people compared with the overall Alberta population. Among the MNA, ASIRs of health service use were higher in rural areas (p < 0.01) and among men (p < 0.01). The injury-related mortality rate was not significantly higher among the MNA compared with the Alberta population. However, among the MNA, Métis males had a significantly higher injury mortality rate than females (p < 0.02)., Conclusion: Results from the current study suggest that injuries are a concern among Métis people. Health planners should design and implement strategies directed to reduce the burden of injury and associated complications for Métis people, especially in rural areas and among Métis males.

The nitrone spin trap 5,5‑dimethyl‑1‑pyrroline N‑oxide (DMPO) dampens endotoxin-induced and TLR4-driven priming of macrophages, but the mechanism remains unknown. The available information suggests a direct binding of DMPO to the TIR domain, which is shared between TLRs. However, TLR2-TIR domain is the only TLR that have been crystallized. Our in silico data show that DMPO binds to four specific residues in the BB-loop within the TLR2-TIR domain. Our functional analysis using hTLR2.6-expressing HEKs cells showed that DMPO can block zymosan-triggered-TLR2-mediated NF-κB activation. However, DMPO did not affect the overall TLR2-MyD88 protein-protein interaction. DMPO binds to the BB-loop in the TIR-domain and dampens downstream signaling without affecting the overall TIR-MyD88 interaction. These data encourage the use of DMPO-derivatives as potential mechanism-based inhibitors of TLR-triggered inflammation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

We describe a case of a 44-year-old woman with locally advanced aggressive angiomyxoma with a novel translocation high-mobility group AT-hook 2-yes-associated protein 1 ( HMGA2-YAP1 ) fusion, implying a t(11;12)(q22.1;q14.3) translocation. She was started on gonadotropin-releasing hormone agonist injection and an aromatase inhibitor for persistent disease, which responded to treatment; she was subsequently treated with radiation before a more definitive operation was conducted. This case report indicates that HGMA2-YAP1- translocated aggressive angiomyxoma is responsive to oestrogen antagonism and hopefully will allow for the development of diagnostics useful for this rare but often morbid neoplasm. This case also highlights the importance of appropriate workup of a soft tissue mass., Competing Interests: Competing interests: RGM has received consulting fees from Foundation Medicine within the last 5 years., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Cadmium (Cd) exposure has been associated with an increased risk of cardiovascular diseases. The diet is a modifiable source of protecting or damaging factors that may affect this risk. Herein we tested the hypothesis that a soybean-based diet (SBD) protects the vascular wall of the aorta against Cd-induced pro-inflammatory and pro-apoptotic effects. To test this hypothesis, we fed male Wistar rats for 60 days with a casein-based diet (CBD) or an SBD. These animals were also exposed to tap-water without (CBD-Co/SBD-Co) or with 15(CBD-15Cd/SBD-15Cd) or 100 (CBD-100Cd/SBD-100Cd) ppm of Cd. Inflammatory parameters (mRNAs and/or proteins) were measured in thoracic aorta tissue. These included inducible and endothelial nitric oxide synthases, cyclooxygenase-2, intracellular-adhesion molecule-1, and vascular cell-adhesion molecule-1. As pro-apoptotic parameters, we measured Bax and Bcl-2 mRNA/protein, as well as TUNEL positive cells in the aorta tissue. Compared to CBD-Co, inflammatory and apoptosis markers increased in the aorta with the concentration of Cd in the drinking water. These effects were not observed in either SBD-15Cd or SBD-100Cd, which were similar to CBD-Co. Cd content in serum and in aortas from animals fed CBD-Co/SBD-15Cd or CBD-Co/SBD-100Cd were similar suggesting that, if any, the effect of SBD is not due to changes in Cd bioaccumulation, but due to secondary effects linked to the composition of the dietary soybean flour. Our findings are consistent with a protective effect of an SBD against Cd-induced inflammation and apoptosis in the thoracic aorta in a rat model., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Objective: To explore self-perceived knowledge and implementation of current opioid guidelines among healthcare providers, and to assess the effect of an opioid-related educational intervention., Design: Pre-post., Setting: Academic., Participants: Sixty-nine participants completed the pre-intervention survey, 45 percent of them also completed a post-survey., Intervention: A short presentation on current opioid guidelines incorporated in a larger accredited continuing professional development (CPD) event., Outcomes: The 5-point Likert scale to express their level of agreement with seven statements was used to estimate their knowledge and implementation of current opioids guideline, along with their self-perceived abilities and level of comfort in prescribing opioids (Moore's conceptual framework)., Results: Fifty percent of the participants were familiar with current opioid prescribing protocols and 46 percent were implementing them, 62 percent stated that were able to identify drug seeking behaviors in patients, 82 percent knew patients' risk factors and 78 percent evaluated them before prescribing opioids, 90 percent indicated that they prescribed non-opioid alternatives, and 35 percent expressed that they feel comfortable prescribing opioids. Self-reported levels of familiarity with the current opioid prescribing protocols ( p < 0.001) and knowledge of patients' risk factors for prescribing opioids ( p = 0.012) increased after the intervention. Improvements in their ability to identify drug seeking behavior in patients ( p = 0.033), and in their comfort prescribing opioids for chronic non-cancer patients ( p = 0.015) were also reported., Conclusions: Healthcare providers' knowledge and implementation of current opioids guidelines need to be strengthened. A single presentation on the opioid crisis and guidelines incorporated within a larger CPD event showed significant gains in self-reported knowledge and skills among healthcare providers.

Background: To assess the effect of an interprofessional educational activity on professional skills, attitudes, and perceived challenges toward obesity management among front-line healthcare providers., Methods: A one-day interprofessional obesity education activity was organized for healthcare providers across various disciplines. All participants were invited to complete an anonymous survey pre- and post-event, and at six-month post-event. The survey was created based on a comprehensive list of perceived skills, professional attitudes and challenges toward obesity intervention compiled from existing literature., Results: Sixty-seven healthcare providers completed the survey pre- and post-event. Participants reported increases in professional skills such as their ability to assess weight (p = 0.04), to address weight management issues (p < 0.001), to teach/motivate patients toward physical activity (p < 0.001) and healthy eating practices (p = 0.001), to use behavior modification techniques (p < 0.001), and to deal with family issues (p < 0.001). Professional attitudes: practitioners felt more educated/competent in obesity management (P < 0.001), learned where to refer patients (p < 0.001), were more comfortable in discussing obesity in managing obesity (p < 0.001), were less likely to avoid the topic (p = 0.004) and felt less frustrated with the low success rate (p = 0.030). Enhancement in professional attitudes remained 6 months after the event. Improvements were mainly associated with male gender, younger age, fewer years of professional practice and healthcare professionals other than physicians. No statistically significant changes in perceived challenges were found after the educational event., Conclusion: Results of this study showed that this interprofessional learning activity contributed to the improvement of professional skills and attitudes of front-line healthcare providers caring for those who are obese or at risk for obesity. The positive results of this interprofessional learning activity aligns with the training needs identified by healthcare practitioners in previous studies, and suggest that this design and content could be used to guide future educational programming in the care of obese people.

Objective: M1-like inflammatory phenotype of macrophages plays a critical role in tissue damage in chronic inflammatory diseases. Previously, we found that the nitrone spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) dampens lipopolysaccharide (LPS)-triggered inflammatory priming of RAW 264.7 cells. Herein, we tested whether DMPO by itself can induce changes in macrophage transcriptome, and that these effects may prevent LPS-induced activation of macrophages., Materials and Methods: To test our hypothesis, we performed a transcriptomic and bioinformatics analysis in RAW 264.7 cells incubated with or without LPS, in the presence or in the absence of DMPO., Results: Functional data analysis showed 79 differentially expressed genes (DEGs) when comparing DMPO vs Control. We used DAVID databases for identifying enriched gene ontology terms and Ingenuity Pathway Analysis for functional analysis. Our data showed that DMPO vs Control comparison of DEGs is related to downregulation immune-system processes among others. Functional analysis indicated that interferon-response factor 7 and toll-like receptor were related (predicted inhibitions) to the observed transcriptomic effects of DMPO. Functional data analyses of the DMPO + LPS vs LPS DEGs were consistent with DMPO-dampening LPS-induced inflammatory transcriptomic profile in RAW 264.7. These changes were confirmed using Nanostring technology., Conclusions: Taking together our data, surprisingly, indicate that DMPO by itself affects gene expression related to regulation of immune system and that DMPO dampens LPS-triggered MyD88- and TRIF-dependent signaling pathways. Our research provides critical data for further studies on the possible use of DMPO as a structural platform for the design of novel mechanism-based anti-inflammatory drugs.

Atypical lipomatous tumor/well-differentiated liposarcoma is the most common sarcoma of soft tissue in adults. We describe the clinical, radiologic, and pathologic features of an atypical lipomatous tumor arising within the soft tissue of the left hand of a 68-year-old female that underwent transformation to dedifferentiated liposarcoma and eventually metastasized. At initial presentation, imaging demonstrated an extensively calcified fatty soft tissue mass with displacement of the digits. Following biopsy and staged debulking, the patient subsequently developed local recurrence, dedifferentiation, and widespread metastases to the lungs, pancreas, bone, and soft tissues. To our knowledge, this is the first case of a cytogenetically proven atypical lipomatous tumor of the hand that has undergone dedifferentiation with widespread metastases.

Single crystals of a new family of layered lanthanide oxychlorides, Ba 3 Ln 2 O 5 Cl 2 (Ln = Gd-Lu), have been synthesized from a molten barium flux. This family crystallizes in the space group I4/mmm (No. 139; Z = 2) with lattice parameters a = 4.3384(1)-4.4541(1) Å and c = 24.5108(7)-24.8448(9) Å. Ba 3 Ln 2 O 5 Cl 2 phases are built up of two different blocks: a perovskite double layer of stoichiometry Ba 2 Ln 2 O 5 formed by corner-connected LnO 5 tetragonal bipyramids and a puckered rock-salt-like interlayer of composition BaCl 2 . A complete structural study along with bond-valence-sum calculations shows that, for lanthanides larger than gadolinium, the structure becomes unstable. Density functional theory calculations show that the valence-band edge is dominated by oxygen orbitals, whereas the conduction band forms from Ba 5d orbitals. The synthesis of this family suggests a route to other potential multianion phases.

Background: Evidence supports the expectation that changes in time of alcohol sales associate with changes in alcohol-related harm in both directions. However, to the best of our knowledge, no comprehensive systematic reviews had examined the effect of policies restricting time of alcohol trading on specific alcohol-related harms., Objective: To compile existing evidence related to the impact of policies regulating alcohol trading hours/days of on specific harm outcomes such as: assault/violence, motor vehicle crashes/fatalities, injury, visits to the emergency department/hospital, murder/homicides and crime., Methods: Systematic review of literature studying the impact of policies regulation alcohol trading times in alcohol-related harm, published between January 2000 and October 2016 in English language., Results: Results support the premise that policies regulating times of alcohol trading and consumption can contribute to reduce injuries, alcohol-related hospitalisations/emergency department visits, homicides and crime. Although the impact of alcohol trading policies in assault/violence and motor vehicle crashes/fatalities is also positive, these associations seem to be more complex and require further study., Conclusion: Evidence suggests a potential direct effect of policies that regulate alcohol trading times in the prevention of injuries, alcohol-related hospitalisations, homicides and crime. The impact of these alcohol trading policies in assault/violence and motor vehicle crashes/fatalities is less compelling., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)