Implementing a Produce Prescription Program in Partnership With a Community Coalition.

Healthy eating reduces risk for chronic disease, but can be out of reach for many Americans experiencing food insecurity. Produce Prescription Programs (PPPs) have emerged as an intervention to address barriers related to fruit and vegetable consumption. Using a social prescribing model, PPPs connect patients with referrals to community resources to reduce barriers to healthy eating. There is evidence of success of PPPs at improving dietary intake, yet little discussion within the literature of practical aspects of implementation. As interest grows around establishing PPPs within communities, increased attention to strategic planning and implementation remains necessary to develop robust and effective programming. We describe implementing the Pontiac Prescription for Health pilot program, highlighting the participatory planning process with partners. Development and implementation included a program model, recruitment methods and materials, a voucher contract and tracking system with produce vendors, physical activity opportunities, culturally competent health education sessions, and evaluation tools. We offer insight into lessons learned and practical implications for future "on-the-ground" planning and implementation. Engaging in a rigorous participatory planning process with all community partners, allowing adequate time to establish service agreements and a voucher system with vendors, and engaging program participants in different ways and spaces throughout the community can enhance program success.

Demographics and perceptions of diversity in dermatopathology workforce and training environments in the United States.

OBJECTIVES: The aim of this study was to determine the demographics and perceptions of diversity, equity, and inclusion (DEI) in the field of dermatopathology to provide a measurable baseline for future efforts to enhance equity measures within our subspecialty. METHODS: A questionnaire based on a previously validated instrument by Association of American Medical Colleges (AAMC) was sent to American Society of Dermatopathology (ASDP) members to collect the demographic information (gender, race, sexual orientation, disability, experience and practice setting, etc.) and evaluate eight diversity, engagement, and inclusivity statements on a 1-5 Likert scale. RESULTS: The demographics of 207 of 1331 (15%) respondents showed slight male predominance. Eleven percent of respondents identified as LGBTQI. The major racial distribution was comprised of 62% White, 18% Asian (including Middle Eastern/Indian), 10% Hispanic, and 4% Black respondents. New-in-practice respondents (those in practice-5 years or less) were more likely to have a pathology background (71% vs. 56%, p = 0.047) than their more-established peers with more than 5 years of service. This trend also contributed to increased diversity in terms of gender (66% females) and race (48% non-White) among the newer generation. Dermatology-trained dermatopathologists were mostly White (70%) and male (53%). Analysis of respondent demographics with perception statements showed that White and US graduate respondents (compared to other groups) were more likely to have a positive perception about DEI within the field of dermatopathology. CONCLUSIONS: The results provide a snapshot of the current state of diversity within the field of dermatopathology. Moreover, these results highlight opportunities for further increasing diversity in general and leadership in particular within dermatopathology.

Anesthesia for Patients Who Self-Report Cannabis (Marijuana) Use Before Esophagogastroduodenoscopy: A Retrospective Review.

Increasing numbers of patients are using cannabis before procedures that require anesthesia. This study set out to examine the impact of cannabis use on anesthetic agent requirements, associated cardiac and respiratory morbidity, and overall satisfaction levels in patients undergoing esophagogastroduodenoscopy (EGD). This involved a retrospective review of patients undergoing EGD at a single center. Fortyseven, self-reported cannabis users were identified and 23 were successfully cross-matched with control participants for comparison purposes. The Wilcoxon signed rank test was used to evaluate differences in propofol administration between the 2 groups, and the McNemar test was used to test for differences in fentanyl and ketamine administration. No statistically significant differences were observed in propofol, fentanyl, or ketamine administration in the cannabis group compared with the control group. No adverse cardiac or respiratory events were reported within 30 days for either group. This study was specific to EGD procedures of short duration, and larger studies are needed to confirm results of no consequence in cannabis users undergoing anesthesia. Future studies should consider cannabis users who undergo anesthesia for diverse procedure types of various durations.

Aging is associated with impaired angiogenesis, but normal microvascular network structure, in the rat mesentery.

A big problem associated with aging is thought to be impaired microvascular growth or angiogenesis. However, to link the evidence for impaired angiogenesis to microvascular dysfunction in aged tissues, we must compare adult vs. aged microvascular networks in unstimulated scenarios. The objective of this study was to test the hypothesis that aged microvascular networks are characterized by both fewer vessels and the impaired ability to undergo angiogenesis. Mesentery tissues from adult (9-mo) and aged (24-mo) male Fischer 344 rats were harvested and immunolabeled for platelet/endothelial cell adhesion molecule (an endothelial cell marker) according to two scenarios: unstimulated and stimulated. For unstimulated groups, tissues harvested from adult and aged rats were compared. For stimulated groups, tissues were harvested 3 or 10 days after compound 48/80-induced mast cell degranulation stimulation. Unstimulated aged microvascular networks displayed larger mean vascular area per tissue area compared with the unstimulated adult networks. The lack of a decrease in vessel density was supported at the gene expression level with RNA-Seq analysis and with comparison of vessel densities in soleus muscle. Following stimulation, capillary sprouting and vessel density were impaired in aged networks at 3 and 10 days, respectively. Our results suggest that aging associated with impaired angiogenesis mechanisms might not influence normal microvascular function, since unstimulated aged microvascular networks can display a "normal adult-like" vessel density and architecture. NEW & NOTEWORTHY: Using a multidimensional approach, we present evidence supporting that aged microvascular networks display vessel density and patterning similar to adult networks despite also being characterized by a decreased capacity to undergo angiogenesis. Thus, vessel loss is not necessarily a characteristic of aging.

Estimation of the Pressure Drop Required for Lymph Flow through Initial Lymphatic Networks.

BACKGROUND: Lymphatic function is critical for maintaining interstitial fluid balance and is linked to multiple pathological conditions. While smooth muscle contractile mechanisms responsible for fluid flow through collecting lymphatic vessels are well studied, how fluid flows into and through initial lymphatic networks remains poorly understood. The objective of this study was to estimate the pressure difference needed for flow through an intact initial lymphatic network. METHODS AND RESULTS: Pressure drops were computed for real and theoretical networks with varying branch orders using a segmental Poiseuille flow model. Vessel geometries per branch order were based on measurements from adult Wistar rat mesenteric initial lymphatic networks. For computational predications based on real network geometries and combinations of low or high output velocities (2 mm/s, 4 mm/s) and viscosities (1 cp, 1.5 cp), pressure drops were estimated to range 0.31-2.57 mmHg. The anatomical data for the real networks were also used to create a set of theoretical networks in order to identify possible minimum and maximum pressure drops. The pressure difference range for the theoretical networks was 0.16-3.16 mmHg. CONCLUSIONS: The results support the possibility for suction pressures generated from cyclic smooth muscle contractions of upstream collecting lymphatics being sufficient for fluid flow through an initial lymphatic network.

Inhibition of COX1/2 alters the host response and reduces ECM scaffold mediated constructive tissue remodeling in a rodent model of skeletal muscle injury.

Extracellular matrix (ECM) has been used as a biologic scaffold material to both reinforce the surgical repair of soft tissue and serve as an inductive template to promote a constructive tissue remodeling response. Success of such an approach is dependent on macrophage-mediated degradation and remodeling of the biologic scaffold. Macrophage phenotype during these processes is a predictive factor of the eventual remodeling outcome. ECM scaffolds have been shown to promote an anti-inflammatory or M2-like macrophage phenotype in vitro that includes secretion of downstream products of cycolooxygenases 1 and 2 (COX1/2). The present study investigated the effect of a common COX1/2 inhibitor (Aspirin) on macrophage phenotype and tissue remodeling in a rodent model of ECM scaffold treated skeletal muscle injury. Inhibition of COX1/2 reduced the constructive remodeling response by hindering myogenesis and collagen deposition in the defect area. The inhibited response was correlated with a reduction in M2-like macrophages in the defect area. The effects of Aspirin on macrophage phenotype were corroborated using an established in vitro macrophage model which showed a reduction in both ECM induced prostaglandin secretion and expression of a marker of M2-like macrophages (CD206). These results raise questions regarding the common peri-surgical administration of COX1/2 inhibitors when biologic scaffold materials are used to facilitate muscle repair/regeneration. STATEMENT OF SIGNIFICANCE: COX1/2 inhibitors such as nonsteroidal anti-inflammatory drugs (NSAIDs) are routinely administered post-surgically for analgesic purposes. While COX1/2 inhibitors are important in pain management, they have also been shown to delay or diminish the healing process, which calls to question their clinical use for treating musculotendinous injuries. The present study aimed to investigate the influence of a common NSAID, Aspirin, on the constructive remodeling response mediated by an ECM scaffold (UBM) in a rat skeletal muscle injury model. The COX1/2 inhibitor, Aspirin, was found to mitigate the ECM scaffold-mediated constructive remodeling response both in an in vitro co-culture system and an in vivo rat model of skeletal muscle injury. The results presented herein provide data showing that NSAIDs may significantly alter tissue remodeling outcomes when a biomaterial is used in a regenerative medicine/tissue engineering application. Thus, the decision to prescribe NSAIDs to manage the symptoms of inflammation post-ECM scaffold implantation should be carefully considered.

An ex vivo model for anti-angiogenic drug testing on intact microvascular networks.

New models of angiogenesis that mimic the complexity of real microvascular networks are needed. Recently, our laboratory demonstrated that cultured rat mesentery tissues contain viable microvascular networks and could be used to probe pericyte-endothelial cell interactions. The objective of this study was to demonstrate the efficacy of the rat mesentery culture model for anti-angiogenic drug testing by time-lapse quantification of network growth. Mesenteric windows were harvested from adult rats, secured in place with an insert, and cultured for 3 days according to 3 experimental groups: 1) 10% serum (angiogenesis control), 2) 10% serum + sunitinib (SU11248), and 3) 10% serum + bevacizumab. Labeling with FITC conjugated BSI-lectin on Day 0 and 3 identified endothelial cells along blood and lymphatic microvascular networks. Comparison between day 0 (before) and 3 (after) in networks stimulated by 10% serum demonstrated a dramatic increase in vascular density and capillary sprouting. Growing networks contained proliferating endothelial cells and NG2+ vascular pericytes. Media supplementation with sunitinib (SU11248) or bevacizumab both inhibited the network angiogenic responses. The comparison of the same networks before and after treatment enabled the identification of tissue specific responses. Our results establish, for the first time, the ability to evaluate an anti-angiogenic drug based on time-lapse imaging on an intact microvascular network in an ex vivo scenario.

Skeletal involution by age-associated oxidative stress and its acceleration by loss of sex steroids.

Both aging and loss of sex steroids have adverse effects on skeletal homeostasis, but whether and how they may influence each others negative impact on bone remains unknown. We report herein that both female and male C57BL/6 mice progressively lost strength (as determined by load-to-failure measurements) and bone mineral density in the spine and femur between the ages of 4 and 31 months. These changes were temporally associated with decreased rate of remodeling as evidenced by decreased osteoblast and osteoclast numbers and decreased bone formation rate; as well as increased osteoblast and osteocyte apoptosis, increased reactive oxygen species levels, and decreased glutathione reductase activity and a corresponding increase in the phosphorylation of p53 and p66(shc), two key components of a signaling cascade that are activated by reactive oxygen species and influences apoptosis and lifespan. Exactly the same changes in oxidative stress were acutely reproduced by gonadectomy in 5-month-old females or males and reversed by estrogens or androgens in vivo as well as in vitro. We conclude that the oxidative stress that underlies physiologic organismal aging in mice may be a pivotal pathogenetic mechanism of the age-related bone loss and strength. Loss of estrogens or androgens accelerates the effects of aging on bone by decreasing defense against oxidative stress.

Osteocyte apoptosis is induced by weightlessness in mice and precedes osteoclast recruitment and bone loss.

UNLABELLED: Mechanical stimulation of cultured osteocytic cells attenuates their apoptosis. We report here that, conversely, reduced mechanical forces in the murine model of unloading by tail suspension increases the prevalence of osteocyte apoptosis, followed by bone resorption and loss of mineral and strength. INTRODUCTION: Mechanical loading is critical for the maintenance of bone mass; weightlessness, as with reduced physical activity in old age, bed rest, or space flight, invariably leads to bone loss. However, the cellular and molecular mechanisms responsible for these phenomena are poorly understood. Based on our earlier findings that physiologic levels of mechanical strain prevent apoptosis of osteocytic cells in vitro, we examined here whether, conversely, reduced mechanical forces increase the prevalence of osteocyte apoptosis in vivo and whether this event is linked to bone loss. MATERIALS AND METHODS: Swiss Webster mice or OG2-11beta-hydroxysteroid dehydrogenase type 2 (OG2-11beta-HSD2) transgenic mice and wildtype littermates were tail-suspended or kept under ambulatory conditions. Static and dynamic histomorphometry and osteocyte and osteoblast apoptosis by in situ end-labeling (ISEL) were assessed in lumbar vertebra; spinal BMD was measured by DXA; and bone strength was measured by vertebral compression. RESULTS: We show that within 3 days of tail suspension, mice exhibited an increased incidence of osteocyte apoptosis in both trabecular and cortical bone. This change was followed 2 weeks later by increased osteoclast number and cortical porosity, reduced trabecular and cortical width, and decreased spinal BMD and vertebral strength. Importantly, whereas in ambulatory animals, apoptotic osteocytes were randomly distributed, in unloaded mice, apoptotic osteocytes were preferentially sequestered in endosteal cortical bone--the site that was subsequently resorbed. The effect of unloading on osteocyte apoptosis and bone resorption was reproduced in transgenic mice in which osteocytes are refractory to glucocorticoid action, indicating that stress-induced hypercortisolemia cannot account for these effects. CONCLUSIONS: We conclude that diminished mechanical forces eliminate signals that maintain osteocyte viability, thereby leading to apoptosis. Dying osteocytes in turn become the beacons for osteoclast recruitment to the vicinity and the resulting increase in bone resorption and bone loss.

Rosiglitazone causes bone loss in mice by suppressing osteoblast differentiation and bone formation.

Because osteoblasts and marrow adipocytes are derived from a common mesenchymal progenitor, increased adipogenesis may occur at the expense of osteoblasts, leading to bone loss. Our previous in vitro studies indicated that activation of the proadipogenic transcription factor peroxisome proliferator-activated receptor isoform gamma 2 with rosiglitazone suppressed osteoblast differentiation. Here, we show that 5-month-old Swiss-Webster mice receiving rosiglitazone for 28 d exhibited bone loss associated with an increase in marrow adipocytes, a decrease in the ratio of osteoblasts to osteoclasts, a reduction in bone formation rate, and a reduction in wall width--an index of the amount of bone formed by each team of osteoblasts. Rosiglitazone had no effect on the number of early osteoblast or osteoclast progenitors, or on osteoblast life span, but decreased the expression of the key osteoblastogenic transcription factors Runx2 and Osterix in cultures of marrow-derived mesenchymal progenitors. These effects were associated with diversion of bipotential progenitors from the osteoblast to the adipocyte lineage, and suppression of the differentiation of monopotential osteoblast progenitors. However, rosiglitazone had no effect on osteoblastic cells at later stages of differentiation. Hence, rosiglitazone attenuates osteoblast differentiation and thereby reduces bone formation rate in vivo, leading to bone loss. These findings provide a mechanistic explanation for the recent evidence that peroxisome proliferator-activated receptor isoform gamma activation is a negative regulator of bone mass and suggest that the increased production of oxidized fatty acids with age may indeed be an important mechanism for age-related osteoporosis in humans.

The skeletal effects of glucocorticoid excess override those of orchidectomy in mice.

Hypogonadism has been implicated as a contributing factor in glucocorticoid-induced osteoporosis, but evidence for this is limited. Hypogonadism and glucocorticoid excess both cause bone loss, but the cellular mechanisms responsible are distinct. Loss of gonadal steroids causes an increase in bone remodeling by up-regulating osteoblastogenesis and osteoclastogenesis. Glucocorticoid excess, conversely, suppresses remodeling by down-regulating osteoblastogenesis and osteoclastogenesis. Nonetheless, both conditions increase osteoblast apoptosis and decrease osteoclast apoptosis, and both cause bone loss due to an undersupply of osteoblasts relative to the need for cavity repair. To investigate their interactions, we compared the effects of orchidectomy, glucocorticoid excess, or both combined in mice. After 28 d, serum unbound testosterone concentration and seminal vesicle weight were not diminished when prednisolone was administered alone. Vertebral bone mineral density and compression strength decreased to the same extent in animals receiving prednisolone or after orchidectomy, but the changes were not additive. Orchidectomy induced the expected up-regulation of osteoblast and osteoclast progenitors, but these changes were prevented in orchidectomized mice simultaneously receiving glucocorticoids. Likewise, the increase in cancellous osteoid, osteoblasts, osteoclasts, bone formation, and activation frequency caused by orchidectomy were prevented by prednisolone. The prevalence of osteoblast apoptosis increased in the mice receiving prednisolone or after orchidectomy, but the increases were not additive. These data demonstrate that hypogonadism does not occur in or contribute to glucocorticoid-induced osteoporosis and that the adverse skeletal effects of glucocorticoid excess override those of orchidectomy.

Glucocorticoids act directly on osteoblasts and osteocytes to induce their apoptosis and reduce bone formation and strength.

Whether the negative impact of excess glucocorticoids on the skeleton is due to direct effects on bone cells, indirect effects on extraskeletal tissues, or both is unknown. To determine the contribution of direct effects of glucocorticoids on osteoblastic/osteocytic cells in vivo, we blocked glucocorticoid action on these cells via transgenic expression of 11beta-hydroxysteroid dehydrogenase type 2, an enzyme that inactivates glucocorticoids. Osteoblast/osteocyte-specific expression was achieved by insertion of the 11beta-hydroxysteroid dehydrogenase type 2 cDNA downstream from the osteoblast-specific osteocalcin promoter. The transgene did not affect normal bone development or turnover as demonstrated by identical bone density, strength, and histomorphometry in adult transgenic and wild-type animals. Administration of excess glucocorticoids induced equivalent bone loss in wild-type and transgenic mice. As expected, cancellous osteoclasts were unaffected by the transgene. However, the increase in osteoblast apoptosis that occurred in wild-type mice was prevented in transgenic mice. Consistent with this, osteoblasts, osteoid area, and bone formation rate were significantly higher in glucocorticoid-treated transgenic mice compared with glucocorticoid-treated wild-type mice. Glucocorticoid-induced osteocyte apoptosis was also prevented in transgenic mice. Strikingly, the loss of vertebral compression strength observed in glucocorticoid-treated wild-type mice was prevented in the transgenic mice, despite equivalent bone loss. These results demonstrate for the first time that excess glucocorticoids directly affect bone forming cells in vivo. Furthermore, our results suggest that glucocorticoid-induced loss of bone strength results in part from increased death of osteocytes, independent of bone loss.

Promotion of osteoclast survival and antagonism of bisphosphonate-induced osteoclast apoptosis by glucocorticoids.

Glucocorticoids depress bone formation by inhibiting osteoblastogenesis and increasing osteoblast apoptosis. However, the role of bone resorption in the initial rapid phase of bone loss characteristic of glucocorticoid-induced osteoporosis is unexplained, and the reason for the efficacy of bisphosphonates in this condition remains unknown. We report that in murine osteoclast cultures, glucocorticoids prolonged the baseline survival of osteoclasts and antagonized bisphosphonate-induced caspase activation and apoptosis by a glucocorticoid receptor-mediated action. Consistent with the in vitro evidence, in a murine model of glucocorticoid-induced osteoporosis, the number of cancellous osteoclasts increased, even though osteoclast progenitor number was reduced. Moreover, in mice receiving both glucocorticoids and bisphosphonates, the expected proapoptotic effect of bisphosphonates on osteoclasts was abrogated, as evidenced by maintenance of osteoclast numbers and, additionally, loss of bone density. In contrast, bisphosphonate administration prevented glucocorticoid-induced osteoblast apoptosis. These results indicate that the early loss of bone with glucocorticoid excess is caused by extension of the life span of pre-existing osteoclasts, an effect not preventable by bisphosphonates. Therefore, the early beneficial effects of these agents must be due, in part, to prolonging the life span of osteoblasts.

Educational outcome for secondary and postsecondary students following traumatic brain injury.

During the 12 month period of January-December 1991, 75 admissions were made to the Head Injury Unit at Bethesda Hospital, Melbourne, Australia. Approximately 26% (20) of these admissions were either secondary or postsecondary students. Thirteen of the 20 students were interviewed by telephone at approximately 3 years postinjury and demographic and medical information were obtained from their medical files. Outcome was documented in three areas: educational, medical and psychosocial status. At 3 years postinjury, 11 subjects (85%) had either completed a course or were still studying. The average time for students to return to study was approximately 11 months postinjury. The students reported a number of changes including: enrollment in different courses, a reduction in course load to part-time study, altered educational and vocational goals and an increased need to utilize study skill strategies, individual tuition and special consideration. In addition, students reported changes to their relationships with peers and their involvement in extracurricular activities. It is apparent from these results that a number of factors need to be considered when a student is planning to return to study following TBI and that a range of support services may be required. Future studies are needed to examine the factors which impede or enhance a student's progress following TBI.