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Neural population dynamics relevant to behavior vary over multiple spatial and temporal scales across three-dimensional volumes. Current optical approaches lack the spatial coverage and resolution necessary to measure and manipulate naturally occurring patterns of large-scale, distributed dynamics within and across deep brain regions such as the striatum. We designed a new micro-fiber array approach capable of chronically measuring and optogenetically manipulating local dynamics across over 100 targeted locations simultaneously in head-fixed and freely moving mice, enabling the investigation of cell-type- and neurotransmitter-specific signals over arbitrary 3D volumes at a spatial resolution and coverage previously inaccessible. We applied this method to resolve rapid dopamine release dynamics across the striatum, revealing distinct, modality-specific spatiotemporal patterns in response to salient sensory stimuli extending over millimeters of tissue. Targeted optogenetics enabled flexible control of neural signaling on multiple spatial scales, better matching endogenous signaling patterns, and the spatial localization of behavioral function across large circuits., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Online programs may help to engage patients in advance care planning in outpatient settings. We sought to implement an online advance care planning program, PREPARE (Prepare for Your Care; http://www.prepareforyourcare.org), at home and evaluate the changes in advance care planning engagement among patients attending outpatient clinics., Methods: We undertook a prospective before-and-after study in 15 primary care clinics and 2 outpatient cancer centers in Canada. Patients were aged 50 years or older (primary care) or 18 years or older (cancer care) and free of cognitive impairment. They used the PREPARE website over 6 weeks, with reminders sent at 2 or 4 weeks. We used the 55-item Advance Care Planning Engagement Survey, which measures behavior change processes (knowledge, contemplation, self-efficacy, readiness) on 5-point scales and actions relating to substitute decision makers, quality of life, flexibility for the decision maker, and asking doctors questions on an overall scale from 0 to 21; higher scores indicate greater engagement., Results: In total, 315 patients were screened and 172 enrolled, of whom 75% completed the study (mean age = 65.6 years, 51% female, 35% had cancer). The mean behavior change process score was 2.9 (SD 0.8) at baseline and 3.5 (SD 0.8) at follow-up (mean change = 0.6; 95% CI, 0.49-0.73); the mean action measure score was 4.0 (SD 4.9) at baseline and 5.2 (SD 5.4) at follow-up (mean change = 1.2; 95% CI, 0.54-1.77). The effect size was moderate (0.75) for the former and small (0.23) for the latter. Findings were similar in both primary care and cancer care populations., Conclusions: Implementation of the online PREPARE program in primary care and cancer care clinics increased advance care planning engagement among patients., (© 2020 Annals of Family Medicine, Inc.)

Rationale: Aging is characterized by functional impairment and reduced capacity to respond appropriately to environmental stimuli and injury. With age, there is an increase in the incidence and severity of chronic and acute lung diseases. However, the relationship between age and the lung's reduced ability to repair is far from established and necessitates further research in the field., Objectives: Little is currently known about age-related phenomena in mesenchymal stem cells (MSCs). On account of their ability to protect the endothelium and the alveolar epithelium through multiple paracrine mechanisms, we looked for adverse effects that aging might cause in MSC biology. Such age-related changes might partly account for the increased susceptibility of the aging lung to injury., Measurements and Main Results: We demonstrated that old mice have more inflammation in response to acute lung injury. To investigate the causes, we compared the global gene expression of aged and young bone marrow-derived MSCs (B-MSCs). Our results revealed that the expression levels of inflammatory response genes depended on the age of the B-MSCs. We demonstrated that the age-dependent decrease in expression of several cytokine and chemokine receptors is important for the migration and activation of B-MSCs. Finally, we showed by adoptive transfer of aged B-MSCs to young endotoxemic mice that aged cells lacked the antiinflammatory protective effect of their young counterparts., Conclusions: Taken together, the decreased expression of cytokine and chemokine receptors in aged B-MSCs compromises their protective role by perturbing the potential of B-MSCs to become activated and mobilize to the site of injury.

Acute respiratory distress syndrome (ARDS) is an important cause of morbidity and mortality, with no currently effective therapies. Several preclinical studies have shown that human mesenchymal stem cells (hMSCs) have therapeutic potential for patients with ARDS because of their immunomodulatory properties. The clinical use of hMSCs has some limitations, such as the extensive manipulation required to isolate the cells from bone marrow aspirates and the heterogeneity in their anti-inflammatory effect in animal models and clinical trials. The objective of this study was to improve the protective anti-inflammatory capacity of hMSCs by evaluating the consequences of preactivating hMSCs before use in a murine model of ARDS. We injected endotoxemic mice with minimally manipulated hMSCs isolated from the bone marrow of vertebral bodies with or without prior activation with serum from ARDS patients. Minimally manipulated hMSCs were more efficient at reducing lung inflammation compared with isolated and in vitro expanded hMSCs obtained from bone marrow aspirates. Where the most important effect was observed was with the activated hMSCs, independent of their source, which resulted in increased expression of interleukin (IL)-10 and IL-1 receptor antagonist (RN), which was associated with enhancement of their protective capacity by reduction of the lung injury score, development of pulmonary edema, and accumulation of bronchoalveolar lavage inflammatory cells and cytokines compared with nonactivated cells. This study demonstrates that a low manipulation during hMSC isolation and expansion increases, together with preactivation prior to the therapeutic use of hMSCs, would ensure an appropriate immunomodulatory phenotype of the hMSCs, reducing the heterogeneity in their anti-inflammatory effect.

Introduction: The acute respiratory distress syndrome (ARDS), affects up to 150,000 patients per year in the United States. We and other groups have demonstrated that bone marrow derived mesenchymal stromal stem cells prevent ARDS induced by systemic and local administration of endotoxin (lipopolysaccharide (LPS)) in mice., Methods: A study was undertaken to determine the effects of the diverse populations of bone marrow derived cells on the pathophysiology of ARDS, using a unique ex-vivo swine preparation, in which only the ventilated lung and the liver are perfused with autologous blood. Six experimental groups were designated as: 1) endotoxin alone, 2) endotoxin + total fresh whole bone marrow nuclear cells (BMC), 3) endotoxin + non-hematopoietic bone marrow cells (CD45 neg), 4) endotoxin + hematopoietic bone marrow cells (CD45 positive), 5) endotoxin + buffy coat and 6) endotoxin + in vitro expanded swine CD45 negative adherent allogeneic bone marrow cells (cultured CD45neg). We measured at different levels the biological consequences of the infusion of the different subsets of cells. The measured parameters were: pulmonary vascular resistance (PVR), gas exchange (PO2), lung edema (lung wet/dry weight), gene expression and serum concentrations of the pro-inflammatory cytokines IL-1β, TNF-α and IL-6., Results: Infusion of freshly purified autologous total BMCs, as well as non-hematopoietic CD45(-) bone marrow cells significantly reduced endotoxin-induced pulmonary hypertension and hypoxemia and reduced the lung edema. Also, in the groups that received BMCs and cultured CD45neg we observed a decrease in the levels of IL-1β and TNF-α in plasma. Infusion of hematopoietic CD45(+) bone marrow cells or peripheral blood buffy coat cells did not protect against LPS-induced lung injury., Conclusions: We conclude that infusion of freshly isolated autologous whole bone marrow cells and the subset of non-hematopoietic cells can suppress the acute humoral and physiologic responses induced by endotoxemia by modulating the inflammatory response, mechanisms that do not involve engraftment or trans-differentiation of the cells. These observations may have important implications for the design of future cell therapies for ARDS.

Purpose/objectives: To identify and describe decision-making influences on men who decide to manage their low-risk prostate cancer with active surveillance., Research Approach: Qualitative, semistructured interview., Setting: The Prostate Centre at Vancouver General Hospital in Canada., Participants: 25 patients diagnosed with low-risk prostate cancer and on active surveillance., Methodologic Approach: An interpretative, descriptive, qualitative design., Main Research Variables: Factors that influenced men's decisions to take up active surveillance., Findings: The specialists' description of the prostate cancer was the most influential factor on men choosing active surveillance. Patients did not consider their prostate cancer to be life threatening and, in general, were relieved that no treatment was required. Avoiding treatment-related suffering and physical dysfunction and side effects such as impotence and incontinence was cited as the major reason to delay treatment. Few men actively sought treatment or health-promotion information following their treatment decision. Female partners played a supportive role in the decision. The need for active treatment if the cancer progressed was acknowledged. Patients were hopeful that new treatments would be available when and if they needed them. Being older and having comorbidities did not preclude the desire for future active treatment. Patients carried on with their lives as usual and did not report having any major distress related to being on active surveillance., Conclusions: The study findings indicate that men are strongly influenced by the treating specialist in taking up active surveillance and planning future active treatments. As such, most men relied on their specialists' recommendation and did not perceive the need for any adjunct therapy or support until the cancer required active treatment., Interpretation: Oncology nurses should work collaborative-ly with specialists to ensure that men receive the information they need to make informed treatment decisions.

Many prostate cancer support groups (PCSGs) have formed in North America during the past decade, yet their operation or factors influencing sustainability are poorly understood. This article reports micro (intragroup), meso (intergroup), and macro (group/structure) analyses drawn from the fieldwork and participant observations conducted for an ethnographic study of PCSGs based in British Columbia, Canada. The findings indicate that effective group leadership is integral to group sustainability and the recruitment and retention of attendees. At the meso level, intergroup connections and communication were often informal; however, the primary purpose of all the PCSGs was to provide information and support to men and their families. Many PCSGs were uncertain how formal associations with cancer fund-raising societies would influence group effectiveness. Macro issues such as prostate cancer activism resided with individual group "champions" through activities coordinated by provincial and national PCSG organizations. However, activism did not guarantee group sustainability. The study findings reveal why some groups flourish while others appear untenable, and form the basis for discussion about how PCSG sustainability might be best achieved.

There are more than 100 prostate cancer support groups (PCSGs) in Canada, most of which meet on a monthly basis-yet little attention has been paid to the role of women at these groups. As part of an ongoing ethnographic study of PCSGs, we examined women's motivations for attending the groups, their ways of functioning in PCSGs and the benefits they accrued. Participant observations conducted at 13 British Columbian-based PCSGs and individual interview data from 20 women who regularly attended PCSG meetings were analyzed. Although the groups did not overtly limit women's attendance, the women's decisions to attend and their participation at group meetings were subject to much self-reflection, uncertainty and tension. Motivations to access a PCSG included a desire to support their partners, develop understandings about the illness and disease, and to manage their own experience of prostate cancer. Our analyses revealed that women assume three roles in PCSGs: social facilitator, background supporter and cancer co-survivor. The women reported many interrelated benefits as a result of attending, including information, hope and reassurance, and connecting with other women in similar circumstances. The results from this study reveal how traditional feminine ideals, such as nurturing and caring for the men in their lives, facilitating social connections and the desire to share emotional experiences guided the behaviors. Based on the study findings, we suggest that efforts to support women's involvement in PCSGs are critical to enhancing the effectiveness of the groups for both men and women.

Men's smoking is largely under-examined despite research that has consistently linked partner smoking to pregnant women's smoking and smoking relapse in the postpartum. An on-going qualitative study involving 31 couples in Canada exploring the influence of couple interactions on women's tobacco reduction provided the opportunity to examine men's smoking in the context of women's tobacco reduction or cessation during pregnancy and postpartum. Individual open-ended interviews with 20 men who smoked were conducted at 0-6 weeks following the birth of their infants and again at 16-24 weeks postpartum. Constant comparative methods were used along with social constructivist perspectives of fatherhood and gender to guide data analysis and enhance theoretical sensitivity. Four themes emerged in men's accounts of their tobacco use: (1) expressing masculinity through smoking, (2) reconciling smoking as a family man, (3) losing the freedom to smoke, and (4) resisting a smoke-less life. Men's reliance on and commitment to dominant ideals of masculinity seemed to preclude them from viewing their partner's tobacco reduction or cessation for pregnancy as an opportunity for cessation. Expectant and new fathers who smoke, however, may be optimally targeted for cessation interventions because it is a time when men experience discomfort with their smoking and when discontinuities in everyday life associated with the transition to fatherhood and presence of a new baby provide opportunities for establishing new routines. Implications for gender-sensitive smoking cessation interventions are discussed.

EMLA Cream (EC; Astra, Westborough, MA) has been widely used as a local anesthetic. Limited safety information is available with respect to the application of EC to the oral mucous membranes. The purpose of this pilot study was to evaluate the efficacy and safety of EC when applied to oral mucosa for fiberoptic intubation. Twenty ASA physical status I-IV patients (11 women and 9 men), 28-57 yr old, who were scheduled for awake, fiberoptic, intubation participated in this open-label study. A total of 4 g of EC was used for 5 min until the patient showed no evidence of a gag reflex (this was evaluated clinically by the patient's acceptance of the William's airway and considered the endpoint for assessing adequate topicalization of the oropharynx). The measured peak plasma concentration of lidocaine or prilocaine did not reach toxic levels in any patient. Methemoglobin levels did not exceed normal values (1.5%) in any patient, and there was no relationship between methemoglobin levels and patient weight, amount of EC used, measured peak plasma concentration, or times to measured peak concentrations of prilocaine or lidocaine. We conclude that EC provided satisfactory topical anesthesia allowing for successful oral fiberoptic intubation in all patients and should be considered a safe alternative for anesthetizing the airway of patients requiring awake oral fiberoptic intubation.

Parents frequently utilize baby walkers in their infants of approximately 5-15 mo of age and create opportunities for traumatic accidents. Healthcare professionals have tried to increase awareness of their dangers; despite this, between 1986 and 1991 reported walker-related accidents rose 45%. We determined if walkers were a significant contributor to childhood poisonings and what toxins were encountered most commonly. A 14-mo prospective study in a regional poison information center determined the prevalence of accidental pediatric poisonings in children aged 5-15 mo old who suffered their exposure while in a baby walker. The regional poison information center managed 7.058 poisoning exposures, 2.8% of which occurred while the child was in an infant walker. The mean age was 8.25 mo (range 5-14 mo), with 96% less than 12 mo. Substances involved were: plants 56.7%, cleaning products 9.9%, cosmetics 5.5%, construction supplies 5.0%, cigarettes 4.5%, topicals 4.5%, oral medications 2.0%, chalk 2.0% and miscellaneous 9.9%. The majority (95%) of children were asymptomatic. Infant walkers contributed substantially less to infant poisonings than was anticipated. Despite the innocuous nature of exposures, a vulnerable population was exposed to potential poisons within reach of their grasp. Baby walker injuries are not limited to trauma, and accidental poisonings should be included in the admonitions that accompany their use.