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While many HIV-positive individuals with "chaotic" lives (e.g. unstable housing, substance use, etc.) have difficulty adhering to their antiretroviral therapy (ART), others have achieved successful adherence. We used focused ethnography to interview 14 HIV-positive individuals to learn why, despite their chaotic lives, they were able to achieve consistent ART adherence. Data revealed that participants felt that while they had little or no control over their life circumstances they recognized that, by taking their ART, they could have control over their HIV. Social services and health care providers must incorporate support for this sense of control in efforts to improve adherence [ABSTRACT FROM AUTHOR]

Background: Menopause and midlife are stages in a woman's life that can be marked by debilitating symptoms and increasing risks for cancer, cardiovascular, metabolic, and bone health issues. Walking represents a simple, low cost, and widely accessible activity with proven health benefits, though its therapeutic effect on alleviating menopause symptoms is not well characterized. Women are generally not opposed to exercise programs; however, increasing or maintaining exercise levels remains a challenge. We undertook a qualitative descriptive study to explore features of a walking program that would be conductive to menopausal women's participation, as well as to inform the development of such a program.Methods: We conducted focus groups with women recruited from two menopause clinics and who suffered from moderate to severe menopause symptoms. The focus groups were audio recorded and transcribed. Women were prompted to talk about their menopause experience and exercise practice and how they would envision a walking exercise program that would keep them engaged. Qualitative content analysis was used to analyze the data and to identify characteristics of a walking exercise program.Results: Twenty women participated in 5 focus groups. Women were very interested in trying walking as a means of staying healthy and possibly reducing menopause symptoms. Four major characteristics emerged as important for a walking program: (a) sensitivity to health realities of menopausal women, (b) inclusivity of various needs/levels of physical ability, (c) attentiveness to the need for mutual social support, (d) flexibility in planning of locations and scheduling. A restricted social network platform with features catering to women in menopause was suggested as suitable to initiate and sustain an adequate walking program.Conclusions: The findings of this study will be essential in designing a program that would be attractive for women to start and maintain a walking habit. The program would assist in elucidating whether walking is a useful and valuable alternative therapy for menopausal symptoms and, ultimately, might help women staying fit in midlife and postmenopausal. [ABSTRACT FROM AUTHOR]

Abstract Cell-to-cell communication between bone, cartilage and the synovial membrane is not fully understood and it is only attributed to the diffusion of substances through the extracellular space or synovial fluid. In this study, we found for the first time that primary bone cells (BCs) including osteocytes, synovial cells (SCs) and chondrocytes (CHs) are able to establish cellular contacts and to couple through gap junction (GJ) channels with connexin43 (Cx43) being dominant. Transwell co-culture and identification by mass spectrometry revealed the exchange of essential amino acids, peptides and proteins including calnexin, calreticulin or CD44 antigen between contacting SCs, BCs and CHs. These results reveal that CHs, SCs and BCs are able to establish intercellular connections and to communicate through GJ channels, which provide a selective signalling route by the direct exchange of potent signalling molecules and metabolites. Highlights • Evidence of biomechanical and molecular signalling between cartilage, subchondral bone and synovial tissue have raised the concept of molecular crosstalk between tissues in the joint. • Chondrocytes, bone cells and synovial cells are able to establish cellular connections and communicate with another via contact between membrane-bound cell surface molecules and gap junction channels mainly formed by connexin43. • Gap junctions between chondrocytes and bone cells can synchronize electrical activity (electrical signals) and may enable metabolic coupling. • The discovery of such communication has potential implications on the mechanisms that regulate the interactions of these cells in health and diseases such as osteoarthritis or rheumatoid arthritis, which involve altered expression of connexin43. [ABSTRACT FROM AUTHOR]

Ageing processes play a major contributing role for the development of Osteoarthritis (OA). This prototypic degenerative condition of ageing is the most common form of arthritis and is accompanied by a general decline, chronic pain and mobility deficits. The disease is primarily characterized by articular cartilage degradation, followed by subchondral bone thickening, osteophyte formation, synovial inflammation and joint degeneration. In the early stages, osteoarthritic chondrocytes undergo phenotypic changes that increase cell proliferation and cluster formation and enhance the production of matrix-remodelling enzymes. In fact, chondrocytes exhibit differentiation plasticity and undergo phenotypic changes during the healing process. Current studies are focusing on unravelling whether OA is a consequence of an abnormal wound healing response. Recent investigations suggest that alterations in different proteins, such as TGF-ß/BMPs, NF-Kß, Wnt, and Cx43, or SASP factors involved in signalling pathways in wound healing response, could be directly implicated in the initiation of OA. Several findings suggest that osteoarthritic chondrocytes remain in an immature state expressing stemness-associated cell surface markers. In fact, the efficacy of new disease-modifying OA drugs that promote chondrogenic differentiation in animal models indicates that this may be a drug-sensible state. In this review, we highlight the current knowledge regarding cellular plasticity in chondrocytes and OA. A better comprehension of the mechanisms involved in these processes may enable us to understand the molecular pathways that promote abnormal repair and cartilage degradation in OA. This understanding would be advantageous in identifying novel targets and designing therapies to promote effective cartilage repair and successful joint ageing by preventing functional limitations and disability. [ABSTRACT FROM AUTHOR]

[Display omitted] • The half-life of 10Panx1 is circa 2 min in human plasma. • Asp8 and Gln3 were pinpointed as critical residues in the inhibition of Pannexin1 channels by 10Panx1. • Proteolytically stable analogues (t 1/2 greater than 24 h) were obtained through the design of a retro-inverso and all-D analogues. • Specific amino acid substitutions lead to analogues with increased in vitro Pannexin1 channel inhibitory capacity as compared to the reference lead sequence 10Panx1. Pannexin1 channels facilitate paracrine communication and are involved in a broad spectrum of diseases. Attempts to find appropriate pannexin1 channel inhibitors that showcase target-selective properties and in vivo applicability remain nonetheless scarce. However, a promising lead candidate, the ten amino acid long peptide mimetic 10Panx1 (H-Trp1-Arg2-Gln3-Ala4-Ala5-Phe6-Val7-Asp8-Ser9-Tyr10-OH), has shown potential as a pannexin1 channel inhibitor in both in vitro and in vivo studies. Nonetheless, structural optimization is critical for clinical use. One of the main hurdles to overcome along the optimization process consists of subduing the low biological stability (10Panx1 t 1/2 = 2.27 ± 0.11 min). To tackle this issue, identification of important structural features within the decapeptide structure is warranted. For this reason, a structure–activity relationship study was performed to proteolytically stabilize the sequence. Through an Alanine scan, this study demonstrated that the side chains of Gln3 and Asp8 are crucial for 10Panx1′s channel inhibitory capacity. Guided by plasma stability experiments, scissile amide bonds were identified and stabilized, while extracellular adenosine triphosphate release experiments, indicative of pannexin1 channel functionality, allowed to enhance the in vitro inhibitory capacity of 10Panx1. [ABSTRACT FROM AUTHOR]

Connexins (Cxs) are integral membrane proteins that form high-conductance plasma membrane channels, allowing communication from cell to cell (via gap junctions) and from cells to the extracellular environment (via hemichannels). Initially described for their role in joining excitable cells (nerve and muscle), gap junctions (GJs) are found between virtually all cells in solid tissues and are essential for functional coordination by enabling the direct transfer of small signalling molecules, metabolites, ions, and electrical signals from cell to cell. Several studies have revealed diverse channel-independent functions of Cxs, which include the control of cell growth and tumourigenicity. Connexin43 (Cx43) is the most widespread Cx in the human body. The myriad roles of Cx43 and its implication in the development of disorders such as cancer, inflammation, osteoarthritis and Alzheimer's disease have given rise to many novel questions. Several RNA- and DNA-binding motifs were predicted in the Cx43 and Cx26 sequences using different computational methods. This review provides insights into new, ground-breaking functions of Cxs, highlighting important areas for future work such as transfer of genetic information through extracellular vesicles. We discuss the implication of potential RNA- and DNA-binding domains in the Cx43 and Cx26 sequences in the cellular communication and control of signalling pathways. [ABSTRACT FROM AUTHOR]

Introduction: Hypermasculine prison culture produces hierarchies based on individuals' ability to assert dominance through strength and violence. Pain can impact physical strength, thereby limiting the ability to elevate or maintain social status within such hierarchies., Aim: The aim of the study was to explore the pain experiences of incarcerated men who were embedded into hypermasculine prison culture., Methods: Interpretive description co-positioned with relational ethics informed the study design. Twelve males participated in 1-hour interviews, which were transcribed verbatim and analyzed inductively to identify themes. The data analysis occurred in three phases: sorting and organizing, making sense of patterns, and transforming patterns into findings., Results: We found that correctional settings were characterized by a social culture of toxic hypermasculinity that influenced the pain experiences of people who were incarcerated. Individuals who experienced pain were more vulnerable to self-isolation in situations in which pain threatened their ability to defend themselves and their previously established social status within the prison hierarchy. Yet, those who felt secure in subordinate hierarchical positions and had effective peer relationships perceived greater safety in communal settings, which proved to be a distraction from pain., Conclusion: In the context of incarceration, positive peer relationships and perceptions of safety positively influenced individuals' experience of pain., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 International Association of Forensic Nurses.)

Recent events, such as the COVID-19 pandemic, have drawn nationwide attention to systemic racism as a serious threat to public health in Canada. One promising approach to address such racism is through developing and implementing standardized procedures for collecting and using disaggregated, race-based data. In this commentary, we summarize why this approach is necessary to address systemic racism in Canada, and highlight municipal actions being taken in Edmonton, Alberta, to move this approach forward. In 2021, a Race-based Data Table, comprising 24 institutions and organizations affiliated with health, education, and policing systems, was formed in Edmonton. It aimed to engage practitioners, systems representatives, academics, and community members in collective advocacy around accessing race-based data to better understand and address disparate health outcomes associated with COVID-19 for racialized communities. Further, the Table intends to co-create a charter and toolkit outlining best practices for ethical, race-based data collection and use with local stakeholders and knowledge users. In documenting the beginning stages of the Table, and in evaluating its ongoing progress, we contribute to national conversations regarding the need for government institutions and other organizations to consistently collect and use race-based data as a means of increasing transparency and accountability in their actions., (© 2024. The Author(s) under exclusive license to The Canadian Public Health Association.)

Background: Individuals experiencing pain while incarcerated depend on nurses, security structures, processes, and regulations for relief., Purpose: The intent of this research was to understand men's experience of pain during incarceration to inform correctional nursing practice., Method: Interpretive description, co-positioned with relational ethics, guided this study. Twelve incarcerated men participated in a single 1-hour interview that was audio-recorded and transcribed. The resultant text was analyzed for themes., Findings: The two main themes were dependence on staff and institutional processes and dependence on oneself and others who were incarcerated. Participants reported a substantial loss in their ability to access pain-relieving medications, products, and services. Unresponsive or delayed pain-relieving interventions from nurses contributed to their sense of indignity, disrespect, and injustice. The participants employed whatever was available, mainly exercise equipment and social support, to manage their pain., Discussion: Nurses must engage with incarcerated patients meaningfully to understand and respond to contextual factors that influence their pain experiences. Participants identified loss of autonomy and dependence on nurses as barriers to their pain relief., Conclusion: Nurse engagement and responsiveness are crucial to altering incarcerated men's perceptions of injustice or helplessness while improving their pain experiences. Nurses must also foster autonomous pain-management approaches that men can use without limitations within correctional settings., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 International Association of Forensic Nurses.)

Abstract: Connexins play a crucial role in the formation of gap junctions that connect cells to each other, as well as cells to the surrounding environment. In recent years, connexin 43 has been extensively studied in various human tumors. In this study, we conducted an immunohistochemical analysis to evaluate the expression of connexin in 16 dermatofibromas (DFs) and 13 dermatofibrosarcoma protuberans (DFSP). Connexin was diffusely expressed in the cytoplasm of all DFs with moderate or strong intensity, whereas all DFSPs showed negative staining. In addition to its diagnostic implications, the loss of Cx43 may elucidate the invasive capacity of DFSP and offer a potential avenue for future therapeutic interventions., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The purpose of this study is to explore the facilitators to integrating complementary therapies in conventional pediatric hospital practice based on the experiences of parents, healthcare providers, and complementary therapy providers., Design: This study is part of a larger research study that examined the introduction of a pediatric integrative medicine service in an acute care children's hospital in Canada. A qualitative descriptive study was conducted using semi-structured one-on-one telephone and in-person interviews with a sample of parents of children, as well as healthcare providers and complementary therapy providers., Results: A total of 50 individuals, from key-stakeholder groups, were interviewed between May 2014 and January 2016. This study identified the following facilitators for the integration of complementary therapies within conventional care: 1) stakeholders' open-mindedness and familiarity with care practices outside of their experiences; 2) stakeholders' open communication, respect for eachothers' roles in the process of care, and appreciation for the role of complementary therapies within conventional medicine; and 3) stakeholders' receptiveness to redefining the meaning of a 'positive outcome' in the context of hospital care., Conclusion: The findings of this study demonstrate that some of the existing barriers to the integration of complementary therapies in conventional hospital care could be mediated by creating an environment where the fundamental value of commitment to patient wellbeing is equally shared by all stakeholders., (Copyright © 2021 Elsevier Inc. All rights reserved.)

During this last decade, the development of prosenescence therapies has become an attractive strategy as cellular senescence acts as a barrier against tumour progression. In this context, CDK4/6 inhibitors induce senescence and reduce tumour growth in breast cancer patients. However, even though cancer cells are arrested after CDK4/6 inhibitor treatment, genes regulating senescence in this context are still unknown limiting their antitumour activity. Here, using a functional genome-wide CRISPR/Cas9 genetic screen we found several genes that participate in the proliferation arrest induced by CDK4/6 inhibitors. We find that downregulation of the coagulation factor IX (F9) using sgRNA and shRNA prevents the cell cycle arrest and senescent-like phenotype induced in MCF7 breast tumour cells upon Palbociclib treatment. These results were confirmed using another breast cancer cell line, T47D, and with an alternative CDK4/6 inhibitor, Abemaciclib, and further tested in a panel of 22 cancer cells. While F9 knockout prevents the induction of senescence, treatment with a recombinant F9 protein was sufficient to induce a cell cycle arrest and senescence-like state in MCF7 tumour cells. Besides, endogenous F9 is upregulated in different human primary cells cultures undergoing senescence. Importantly, bioinformatics analysis of cancer datasets suggest a role for F9 in human tumours. Altogether, these data collectively propose key genes involved in CDK4/6 inhibitor response that will be useful to design new therapeutic strategies in personalised medicine in order to increase their efficiency, stratify patients and avoid drug resistance., (© 2022. The Author(s).)

Objective: The purpose of this study was to understand emerging roles of parents of hospitalized children with life threatening conditions and to explore how complementary therapies integrated into conventional pediatric care may shift and/or support these roles., Design: This study is part of a larger research study that examined the introduction of a pediatric integrative medicine service at an acute care children's hospital in Canada. A qualitative descriptive study was conducted using one-on-one telephone interviews with a sample of parents of children included in the larger study. Children had access to complementary therapies including Reiki, massage therapy, and acupuncture., Results: A total of 36 interviews were conducted between May 2014 and January 2016. This study found that parents of hospitalized children assume complex roles including that of caregiver, expert and patient (due to high levels of stress and anxiety). Moreover, the study reveals that the integration of complementary therapies with conventional care supports these parental roles., Conclusion: This study reveals that complementary therapies, introduced as a part of integrated approach to pediatric hospital care, and aimed primarily at managing distressing symptoms in patients, had simultaneously a positive contribution in providing parents with the means to navigate the complexities of parenting in the pediatric oncology and cardiology hospital wards and addressing some of their own needs., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Benign cutaneous tumors with follicular differentiation are alleged to differentiate toward parts of the hair follicle. Connexin 43 (Cx43) is a gap junction protein, the tumoral role of which has been investigated in several types of tumors., Objective: To study the pattern of expression of Cx43 in benign cutaneous tumors with follicular differentiation and to compare it with that shown by their alleged anatomical counterparts of the hair follicle., Materials and Methods: Five cases each of trichofolliculoma, trichilemmoma, fibrofolliculoma/trichodiscoma, trichoblastoma, trichoepithelioma, pilomatrixoma, and proliferating trichilemmal tumor, 3 cases of pilar sheath acanthoma, and 1 case of tumor of the follicular infundibulum were examined. Anti-Cx43 antibody was used., Results: Cx43 was expressed by all follicular tumors studied. Comparisons between trichoblastoma and trichoepithelioma and their respective normal counterparts could not be made. In 3 tumors (trichofolliculoma, pilomatrixoma, and the spectrum fibrofolliculoma/trichodiscoma), there was a parallelism between their Cx43 expression pattern and that of their alleged anatomical counterparts. In pilar sheath acanthoma, trichilemmoma, and the tumor of the follicular infundibulum, we only found partial similarities in Cx43 expression. Only the proliferating trichilemmal tumor showed a discordant pattern of expression., Conclusions: Cx43 expression is preserved in benign cutaneous tumors with follicular differentiation and the patterns of Cx43 expression in benign cutaneous tumors with follicular differentiation parallel those of their alleged anatomical counterparts in 5 types (either totally or partially). This preservation might be related to the good behavior of the entities studied.

Background: Pediatric integrative medicine (PIM) refers to the combination of treatments from conventional medicine and complementary therapies for which there is evidence of safety and effectiveness. As pediatric use of complementary therapies increases, it is important to determine parental views on the use of these therapies by their children., Objective: To describe parental experiences with a PIM service for management of pain, nausea/vomiting and anxiety in the context of an inpatient pediatric cardiology unit., Design: Telephone interviews were carried out with the parents of pediatric cardiology inpatients. The interviews focused on their and their child's experiences with the PIM service while in the hospital. Interviews were transcribed, and analyzed using qualitative content analysis., Results: Data saturation was reached after nine interviews conducted during the period between June 2015 and January 2016. Parents self-reported that the PIM service was particularly helpful at alleviating symptoms of anxiety in their children. Moreover, because their children were more at ease, parents also felt less anxiety., Conclusion: Pediatric integrative medicine as an adjunct to conventional care is seen as beneficial by parents of children admitted to a pediatric cardiology unit., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Literature suggests interprofessional education (IPE) and education about complementary therapies for health sciences students may be effectively combined., Methods: A novel 30-hour, 10-week course for interprofessional undergraduate health sciences students combining IPE and complementary therapies learning objectives was developed and offered in 2012 (N = 71), 2013 (N = 120) and 2014 (N = 140). Pre-post mixed methods measurement occurred in three groups: one taking combined IPE-complementary therapies curriculum, and two control groups (one following non-specialized IPE curriculum, and one following combined IPE-continuing care curriculum). The students' attitudinal changes towards IPE and complementary therapies, and their comfort collaborating with students in other health sciences programs were measured using scales. Qualitative evaluation was conducted via content analysis of team-based reflective essays of their opinions towards what they learned about IPE and complementary therapies, and how it changed during the course., Results: Quantitative results exhibited ceiling effects, revealing little change or difference between groups on all measures, with the exception of the Health Professional Collaborative Competency Perception Scale which indicated the students taking the IPE-complementary therapies course reported increased comfort collaborating in comparison with control groups. Qualitative results indicated students: increased their awareness and knowledge about complementary therapies, and were inspired to learn more, appreciated the need for collaboration and communication, desired to be more patient-centered, and wove concepts related to IPE and complementary therapies together., Conclusion: Combining IPE initiatives and basic complementary therapies education can save curricular time, and develop healthcare professionals who appear to be more ready to provide team-based, patient-centered care., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Some pediatric tertiary care centres in North America supplement conventional care with complementary therapies, together known as pediatric integrative medicine (PIM). Evidence to support the safety and efficacy of PIM is emerging, but the cost-effectiveness of an inpatient PIM service has yet to be assessed., Methods/design: This study is a pragmatic cluster controlled clinical trial. Usual care will be compared to usual care augmented with PIM in three pediatric divisions; oncology, general medicine, and cardiology at one large urban tertiary care Canadian Children's Hospital. The primary outcome of the feasibility study is enrolment; the primary outcome of the main study is cost-effectiveness. Other secondary outcomes include the prevalence and severity of key symptoms (i.e. pain, nausea/vomiting and anxiety), efficacy of PIM interventions, patient safety, and parent satisfaction., Discussion: This trial will be the first to evaluate the comparative effectiveness, both clinical and cost, of a PIM inpatient service. The evidence from this study will be useful to families, clinicians and decision makers, and will describe the clinical and economic value of PIM services for pediatric patients admitted to hospital.

Background: Community-based participatory research (CBPR) is "a collaborative process that equitably involves all partners in the research process and recognizes the unique strengths that each brings." Yet working collaboratively throughout the research process is easier said than done., Objectives: To illustrate what happens when community partners' and research partners' "unique strengths" or ways of working collide, and the lessons learned from the process partners used to work through their differences., Methods: An exploratory qualitative method was used to answer the research question, "How do community and research partners resolve conflict embedded in conventional community and research practices?", Lessons Learned and Conclusions: When new partners join an established CBPR partnership, it is important to begin by getting to know the new partner rather than with the tasks that need to be accomplished. Furthermore, when conflict is pervasive, partners should move away from discussions and work together on a concrete task together.