Hope has been associated with increased pain tolerance  and has been incorporated in interventions targeting chronic pain . Research suggests that African Americans with osteoarthritis (OA) pain experience greater pain severity and disability compared to non-Hispanic White individuals . Although the literature is limited, there is some evidence to suggest racial/ethnic differences in hope . The current study examined race as a moderator of the association between hope and pain in a sample of older adults. Experience sampling (ESM) data was used from a multi-site study examining non-Hispanic White and African American individuals with knee osteoarthritis (OA). Participants completed the Adult Hope Scale  during baseline interviews and self-reported momentary pain during 28 ESM calls. Multilevel models revealed a significant interaction between hope and race (p = .04). Specifically, greater hope was associated with decreased momentary pain, and this association was stronger for African American compared to non-Hispanic White individuals. Results suggest that high levels of hope may be particularly protective for African American chronic pain patients. These findings can help inform existing and future interventions focused on enhancing hope in chronic pain populations.


Spinal cord injury (SCI) results in multiple pathophysiological processes, including blood–spinal cord barrier disruption, hemorrhage/ischemia, oxidative stress, neuroinflammation, scar formation, and demyelination. These responses eventually lead to severe tissue destruction and an inhibitory environment for neural regeneration.cAMP signaling is vital for neurite outgrowth and axonal guidance. Stimulating intracellular cAMP activity significantly promotes neuronal survival and axonal regrowth after SCI.However, neuronal cAMP levels in adult CNS are relatively low and will further decrease after injury. Targeting cAMP signaling has become a promising strategy for neural regeneration over the past two decades. Furthermore, studies have revealed that cAMP signaling is involved in the regulation of glial cell function in the microenvironment of SCI, including macrophages/microglia, reactive astrocytes, and oligodendrocytes. cAMP-elevating agents in the post-injury milieu increase the cAMP levels in both neurons and glial cells and facilitate injury repair through the interplay between neurons and glial cells and ultimately contribute to better morphological and functional outcomes. In recent years, combination treatments associated with cAMP signaling have been shown to exert synergistic effects on the recovery of SCI. Agents carried by nanoparticles exhibit increased water solubility and capacity to cross the blood–spinal cord barrier. Implanted bioscaffolds and injected hydrogels are potential carriers to release agents locally to avoid systemic side effects. Cell transplantation may provide permissive matrices to synergize with the cAMP-enhanced growth capacity of neurons. cAMP can also induce the oriented differentiation of transplanted neural stem/progenitor cells into neurons and increase the survival rate of cell grafts. Emerging progress focused on cAMP compartmentation provides researchers with new perspectives to understand the complexity of downstream signaling, which may facilitate the clinical translation of strategies targeting cAMP signaling for SCI repair. Spinal cord injury (SCI) is a devastating neural trauma with an incidence of 54 patients per million people in the United States , the subacute phase (2 days to 2 weeks), the intermediate phase (2 weeks to 6 months), and the chronic phase (>6 months) , which include nine transmembrane members  and one soluble member . tm-ACs are downstream effectors of G-protein coupled receptors (GPCRs) that are activated by extracellular molecules, AC1 and AC8 are also directly activated by Ca2+. sAC is activated by intracellular bicarbonate, Ca2+, and ATP , and oligodendrocyte-myelin glycoprotein (OMgp)  and thereby induce Arg-1 (an M2 macrophage biomarker) expression  tend to exhibit lower GFAP expression and a preserved nonreactive morphology with slender processes, indicating that the increase in Epac2 activity might attenuate the activation of astrocytes. As observed in ex vivo SCI models, S-220-treated spinal cords show a closer relationship between neurite profiles and astrocyte processes, whereas nontreated spinal cords exhibit collapsed growth cones when confronted with RAs  are activated to become reactive astrocytes (RAs) that exhibit cellular hypertrophy and extended processes. RAs subsequently migrate to the periphery of the lesion site, express cell adhesion molecules, and ultimately transform into scar-forming astrocytes (SAs) that adhere to each other to form the glial scars , neural stem and progenitor cells (NSPCs), bone marrow stromal cells (MSCs), and olfactory ensheathing cells (OECs). These cell grafts provide permissive matrices to synergize with the cAMP-induced inherent growth capacity of neurons. Researchers previously injected Schwann cells and db-cAMP into the lesion site of SCI models and delivered rolipram subcutaneously for 2 weeks. The combination treatment significantly promoted axonal regeneration growth and myelination, leading to improved motor function recovery  further investigating the roles of cAMP signaling in different cells, particularly glial cells, under physiological and pathological conditions; (2) promoting the entry of combination strategies into preclinical or clinical trials to further confirm their safety and efficacy; and (3) comprehensively elucidating cAMP compartmentalization to more precisely modulate spatiotemporal intracellular cAMP signaling. All of these efforts will promote the development of new therapeutic strategies for SCI and ultimately benefit the patients.GZ and JG wrote the manuscript. ZW drew the figures. SH and YL helped write the manuscript and reviewed the manuscript. All authors reviewed and approved the final manuscript. All authors contributed to the article and approved the submitted version.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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Determining ways to improve hip fracture recovery in older adults is important, however recruitment of this target population into clinical trials is challenging. Multimodal interventions that target multiple mechanisms of recovery may improve outcomes, but each component presents unique recruitment barriers. While exercise interventions have been shown to be beneficial for hip fracture recovery, offering exercise following completion of conventional physical therapy can be viewed as a burdensome time commitment. Hormone replacement therapy may hold promise for overcoming anabolic resistance, but concern about adverse side effects can also deter participation. STEP-HI is a multisite trial testing whether exercise and testosterone can improve hip fracture recovery in older women. In this talk, recruitment barriers experienced in STEP-HI and strategies employed to overcome these barriers will be discussed. Strategies include: partnering with hospitals, skilled nursing facilities and orthopedic surgeons. providing talks and education materials; and featuring past participant testimonials in recruitment materials.


Researchers are encountering increasing challenges in recruiting participants for healthcare research. We conducted semi-structured individual interviews to identify participant barriers to research and recommendations for overcoming these challenges. We recruited 17 patients and eight caregivers who were approached to participate in a randomized control trial. We also recruited 31 primary care physicians. Using grounded theory, three researchers independently coded the transcripts and then met to compare codes and reconcile discrepancies. Themes from patient and caregiver interviews included time constraints, privacy concerns, lack of research familiarity, disconnect with research institution, self-perceived health status, and concerns with study randomization and repetitive questions. Physician-identified barriers focused on time constraints and study randomization. Patient and caregiver recommendations for study recruitment included various recruitment techniques. Physician recommendations were related to incentives. Although patients and caregivers prefer that their physicians recruit them for health-related research studies, physicians identified time constraints as a barrier to research involvement.


This systematic review aims to evaluate the effect of nicotine replacement therapies (NRTs) on measures of agitation amongst nicotine-dependent adult psychiatric inpatients.Since the introduction of the smoke-free policy for all psychiatric facilities, a psychiatric admission is likely to upset a nicotine-dependent individual's normal routine of nicotine consumption. In addition to the physiological effects of nicotine withdrawal (NW), the interpersonal dynamic which nurse-led guardianship of nicotine products constructs presents stressors to the nicotine dependent patient.Several systematic reviews evaluating changes in objective measures of agitation amongst smoking patients in medical critical care units have found varied results, with some demonstrating worsening agitation with NRT use. We therefore believe that there is sufficient equipoise in the use of NRT to prompt a review of studies amongst psychiatric inpatients.This review identified English language studies through developed search strategies in PubMed/MEDLINE, EMBASE, PyschINFO, PSYCHLit, Cochrane databases, and Google scholar. The bibliographies of notable papers were explored. Hand searches of five major psychiatric journals were conducted. Peer reviewed studies of any study design were included if they reported primary data of adult psychiatric inpatients. Studies were extracted from 1990 – present, this was felt appropriate as nicotine replacement patches became available in 1992.Search strategies were informed by MeSH search terms and included multiple conceptions of “agitation”, including variations on; agitation, irritability, and arousal to capture the concept from broad academic constructions. The quality of studies was assessed with the Newcastle-Ottawa and Cochrane Collaboration tools.This review follows PRISMA guidelines, and an application for PROSPERO registration has been submitted pending acceptance.Two studies were identified which matched inclusion criteria. A double-blinded randomised placebo-controlled trial of 40 nicotine-dependent inpatients from Allen et al. reported a significant 23% reduction in Agitated Behaviour Scores at 24 hours following NRT administration on admission compared to their matched placebo controls. Yet a retrospective cross-sectional analysis from Okoli using scores for NW identified more severe withdrawal symptoms including “restlessness” and “anger/irritability” than nicotine-dependent patients not provided with NRT.Despite considerable commentary within literature there is presently only one study providing moderate evidence of a positive benefit to measures of agitated behaviour from the use of NRT amongst nicotine-dependent psychiatric inpatients. There is currently very low evidence whether NRT improves or exacerbates the agitation associated with NW amongst nicotine-dependent psychiatric inpatients.


Robust evidence of fetal programming of adult disease has surfaced in the last several decades. Human and preclinical investigations of intrauterine insults report perturbations in placental nutrient sensing by the mechanistic target of rapamycin (mTOR). This review focuses on pregnancy complications associated with placental mTOR regulation, such as fetal growth restriction (FGR), fetal overgrowth, gestational diabetes mellitus (GDM), polycystic ovarian syndrome (PCOS), maternal nutrient restriction (MNR), preeclampsia (PE), maternal smoking, and related effects on offspring birthweight. The link between mTOR-associated birthweight outcomes and offspring metabolic health trajectory with a focus on sexual dimorphism are discussed. Both human physiology and animal models are summarized to facilitate in depth understanding. GDM, PCOS and fetal overgrowth are associated with increased placental mTOR, whereas FGR, MNR and maternal smoking are linked to decreased placental mTOR activity. Generally, birth weight is reduced in complications with decreased mTOR  and higher with increased mTOR . Offspring display obesity or a higher body mass index in childhood and adulthood, impaired glucose and insulin tolerance in adulthood, and deficiencies in pancreatic beta-cell mass and function compared to offspring from uncomplicated pregnancies. Defining causal players in the fetal programming of offspring metabolic health across the lifespan will aid in stopping the vicious cycle of obesity and type II diabetes. Decades of research have revealed that many diseases diagnosed over a lifetime have fetal origins. As a response to various exposures during the developmental period, such as maternal over/under-nutrition, chemicals, and stresses, fetal organs may be mal-programmed due to their inherent plasticity during development. The concept of fetal programming suggests that nutritional and environmental events that occur during critical periods of pregnancy cause permanent effects on the fetus and the long-term health trajectory of the offspring. A robust and important area of research investigating the developmental origins of health and disease (DOHAD) hypothesis has made huge strides in understanding the fetal programming of adult chronic and non-communicable diseases. Myriad epidemiological studies provide evidence of this association as it relates to risk for obesity, hypertension, cardiovascular disease, and diabetes ,2. HowevMechanistic target of rapamycin (mTOR) is a serine/threonine kinase that serves as a core component of mTOR complex 1 and mTOR complex 2. mTOR is activated by growth receptors, such as insulin growth factor (IGF) and insulin receptors, via IRS and the PI3K cascade. Direct downstream targets phosphorylated by mTOR include ribosomal protein S6/S6K1 and 4E-BP1, both involved in protein synthesis, ULK1, which inhibits autophagy, and others see . Newer sMaternal-placental-fetal units act in coordination to meet the needs of the fetus and to support the mother simultaneously. Within this coordinated system, mTOR senses and integrates nutrient signals ,8. As suThis narrative review will focus on the relationship between alterations in placental mTOR signaling associated with intrauterine complications and offspring metabolic health. First, placental mTOR signaling and associated birth weight outcomes will be reviewed for each pregnancy complication, with a special focus on sexual dimorphism within each pregnancy complication if data are available. Subsequently, the offspring metabolic health trajectory will be evaluated through discussions of obesity, insulin sensitivity, and pancreatic beta-cell mass and function. Human pathophysiology is reviewed with discussion of important animal studies to better facilitate readers’ understanding.Fetal growth restriction (FGR) is defined as fetal weight below the 10th percentile for gestational age. FGR affects up to 10% of all pregnancies in the United States and carries an increased risk of perinatal mortality and morbidity. Long-term FGR complications include higher risk for hypertension, cardiovascular disease and type II diabetes . FGR invIn human pregnancies, mTOR activity has been shown to be decreased in placentas of FGR/growth-restricted babies . AlteredFGR itself is biased toward males in the human context . In factMaternal obesity during pregnancy elevates the risk of pregnancy complications and large-for-gestational-age babies . SituatiA Swedish study revealed a positive correlation between maternal BMI during the first trimester of pregnancy, birth weight, and placental insulin and mTOR signaling. These findings were accompanied by an inverse correlation between birth weight and AMPK signaling . These dMale sex has been defined as an independent risk factor for macrosomia or fetal overgrowth in humans , perhapsmTOR signaling is a key pathway in mediating maternal-fetal nutrient transport as described above . BrieflyA study of human GDM placentas showed increased mTOR signaling as determined by phosphorylated p70S6K (downstream mTOR target) in GDM compared to normal term placentas . Other sMetformin treatment for GDM introduces another aspect to placental mTOR regulation during pregnancy. Metformin is an anti-diabetic medication commonly prescribed to women with GDM that targets AMPK and subsequently blunts mTOR signaling. Metformin can be transported into fetal blood circulation. Therefore, mTOR signaling in the placenta and developing fetus can be reduced in response to metformin treatment for GDM. In human studies, metformin-exposed offspring are at increased risk for fetal growth restriction and catch-up growth during mid-childhood . In a muGDM is associated with higher birth weight and increased risk for macrosomia , with 15Polycystic ovary syndrome (PCOS) is an endocrine disorder that commonly affects women of reproductive age. Obesity and insulin resistance commonly characterize PCOS and can present PCOS mothers with an increased risk for GDM and hypertension . PCOS moLimited human studies have assessed the direct relationship between placental mTOR, PCOS and pregnancy outcomes. One study addressed whether mTOR signaling was increased in PCOS placentas from uncomplicated pregnancies. However, this study found no effect on mTOR signaling in the PCOS placenta versus controls . In a stHuman and preclinical studies segregating results by sex are lacking in PCOS.Maternal nutrient restriction (MNR) is a phenomenon leading to placental insufficiency and FGR. MNR captures both low protein diets and calorie restriction. Perhaps the most striking evidence linking human MNR to placental insufficiency is the 1944–1945 Dutch Famine, where severe calorie restriction during critical periods of pregnancy resulted in low birth weights and reduced placenta masses .In a baboon model, MNR reduced fetal weights by 13%. This reduction in weight was accompanied by a decrease in placental mTOR signaling  and AKT/insulin signaling  as determined by Western blot analysis . A rat sRoseboom et al., 2011 reported sexual dimorphic effects in severity of reduction of placental size and area in the Dutch Famine cohort. The effect of MNR during the Dutch Famine on the placental area was more severe for male offspring compared to female . PreclinPreeclampsia (PE) is a hypertensive disorder that occurs during pregnancy. Human studies have presented mixed results surrounding the relationship between PE and birth weight.Human placentas from pregnancies complicated by PE exhibit a mild decrease in phosphorylated mTOR but an increase in downstream phosphorylated 4E-BP1 . A signiMild PE has been associated with normal fetal growth of male offspring and growth restriction of female offspring at neonatal stage . A potenThe Centers for Disease Control and Prevention estimate that 12% of women smoke during pregnancy in the United States. Maternal smoking is associated with lower birth weight. For example, an analysis of the Tasmanian Infant Health Survey revealed that maternal prenatal smoking was associated with lower placental and birth weight . The HeaA preclinical model determined that dams exposed to secondhand smoke for 4 days had offspring with decreased placental and fetal weights (FGR), decreased trophoblast invasion, and decreased activation of placental phospho-mTOR, phospho-p70 and phospho-4E-BP1 .Maternal smoking during pregnancy has adverse impacts on fetal programming and offspring health. However, there is a lack of preclinical models of smoking, which limits our understanding of causal factors. In addition, a need for stratification by sex in human investigations and mechanism-driven studies with sex as a biological variable are needed to determine whether there is a sexual dimorphic effect of maternal smoking on offspring metabolic health and resilience.The relationship between birth weight and risk for obesity across the lifespan is well-established. Several findings indicate higher BMI in childhood and adulthood in the offspring of mothers with pregnancy complications. Placental mTOR has been implicated in programming offspring tissues to be more sensitive to a metabolic challenge .Observational studies suggest that the offspring of GDM mothers are more likely to develop childhood obesity (or higher BMI) compared to offspring not exposed to maternal hyperglycemia. This finding has been repeated in several studies across the globe . HoweverSeveral epidemiological studies have reported an association between maternal smoking and childhood/adolescent obesity ,71, possYoung adult males from the Dutch Famine cohort were at greater risk of developing obesity following exposure to nutrient restriction in utero. This finding was specific to enduring severe under-nutrition during first half of pregnancy . SimilarDirect mTOR deletion in the placenta resulted in offspring with obesity outcomes that were different between sexes. Neither male nor female offspring with placental mTOR knockout developed obesity when subjected to a normal chow diet  for 12-weeks. However, when metabolically challenged with a high-fat diet , females became more obese as compared to littermate controls, whereas male offspring on a high-fat diet did not develop obesity [Multiple pregnancy complications are associated with reduced placental mTOR signaling and low birth weight. Low birth weight also has a connection to insulin resistance in adulthood. Due to the timescale needed to study the development of insulin resistance in adulthood, there are limited human studies investigating this relationship in a longitudinal manner. However, evidence from the Dutch Famine cohort and preclinical models have substantiated this relationship .Individuals from the Dutch Famine cohort have reported low birth weight due to prenatal exposure to under-nutrition. In adulthood, this cohort displays impaired glucose tolerance and insulin resistance possibly related to inadequate insulin secretion or action . AnotherA 2002 study was the first to link maternal smoking to development of early adult-onset diabetes . Since tFemale offspring with placental mTOR knockout in utero displayed high-fat diet-induced insulin intolerance in adulthood, accompanied by hyperinsulinemia. On the other hand, male offspring with placental mTOR knockout had comparable glucose and insulin tolerances to littermate controls .Determining the relationship between placental mTOR and offspring pancreatic beta-cell mass and function comprises a newer area of research. Direct placental mTOR knockout gives rise to sexually dimorphic effects on beta-cell mass compensation, discussed in more detail below. The relationship between intrauterine insults such as preeclampsia and nutrient restriction, which have previously been associated with altered mTOR signaling in the placenta, have been studied in the RUPP model of preeclampsia and in maternal low-protein diet investigations ,59.In the gestational hypertension RUPP model, increased beta-cell death, reduced beta-cell area, and decreased mTOR protein level in the offspring fetal pancreas were reported . In respDirect ablation of placental mTOR reduced placental weight in the female offspring but did not alter beta-cell mass in both male and female neonates. Adult female and male offspring showed normal glucose homeostasis under a normal chow diet. While adult female offspring with mTOR knockout in utero demonstrate high-fat diet-induced insulin resistance, they have normal beta-cell mass and function compared to littermate controls .Differences in placental and fetal gene expression, epigenetic mechanisms, and hormone levels have been identified early in fetal development. Dearden et al., in 2018, elegantly reviewed several mechanisms mediating sexual dimorphic programming leading to adult metabolic disruption . DespiteThe importance of mTOR signaling in the placenta to regulate fetal development and programming of metabolic organs is gaining momentum. The link between perturbed placental mTOR and adverse birth weight outcomes has been assessed in several pregnancy complications, and a robust relationship between birth weight and offspring metabolic health trajectory has been defined. However, longitudinal studies and mechanistic investigations are lacking in the current body of research. Longitudinal human studies, as well as preclinical studies designed to follow mother and offspring from pre-conception, through gestation, and across the lifespan are needed to draw causal conclusions. Mechanistic studies investigating molecular changes occurring in response to placental mTOR perturbations both locally in the placenta and systemically throughout the developing fetus will be necessary to understand the sexual dimorphic metabolic outcomes observed. In addition to those highlighted in the previous section, several other mechanisms mediating sexual dimorphism include alterations in inflammation, nutrient transport, and hypoxia in the placenta and developing fetal tissues.


In 2016, catastrophic flooding in south Louisiana claimed 13 lives with billions of dollars in damage to homes and communities in the decade after Hurricanes Katrina and Rita devastated the US Gulf Coast. In this study, we tested the inoculation hypothesis which predicts that older adults will be less distressed than younger adults due to their prior experience with severe weather events. Participants were 218 predominately middle-aged and older adults who varied in current and prior flood experience: less than half (40%) did not flood in 2016, 31% had flood damage, and 29% had relocated permanently inland after catastrophic losses in the 2005 Hurricanes Katrina and Rita and they flooded again in 2016. Depression symptoms were assessed with the 9-item Patient Health Questionnaire (PHQ-9). Emotion regulation strategies were measured using the Cognitive Emotion Regulation Questionnaire-Short Form. Results indicated that the older adults had fewer symptoms of depression and were less likely to report self blame for flood-related adversities compared to younger adults. The two age groups did not differ significantly on the emotion regulation strategies of acceptance, reappraisal, positive refocusing, other blame, and perseveration. Age was inversely associated with symptoms of depression and the maladaptive strategies of self blame for flood-related misfortune and perseveration over losses. These data support the inoculation hypothesis and suggest that prior severe weather experiences, which are likely for older adults living in hurricane prone areas, are important for post-flood resilience. Implications of these findings for disaster planning and age-sensitive interventions to mitigate adversity are considered.


Bilateral giant inguinoscrotal hernia (GIH) is rare and creates significant challenge in surgical management. The main concern of hernia reduction to abdominal cavity is development of abdominal compartment syndrome (ACS). Different approaches for prevention of ACS after surgery have been suggested.We report a case of 68-year-old male with bilateral inguinoscrotal hernia for 20 years reaching just below midpoint of thigh. He presented with difficulty in micturition and mobility. Preoperative investigations were normal. He underwent bilateral mesh repair without any preoperative or intraoperative adjunct measures. No significant complication occurred in postoperative period.Bilateral GIH is rare and the patients usually present late. GIH has been classified into three types on the basis of extension. Type I GIH can be managed with simple hernioplasty, in both unilateral and bilateral cases. Measures like resection of hernia contents and measures to enlarge intraabdominal space are warranted in type II and III GIH. Abdominal volume can be increased by utilising techniques like Pre-operative Progressive Pneumoperitoneum (PPP), injection of Botulinum toxin A (BTA) in the anterior abdominal wall, and rotation of viable tissue. The measures can be used either alone or in combination.Type I GIH can be treated with simple hernioplasty with safety with monitoring for features of ACS and respiratory complications postoperatively. However, additional measures like resection of hernia contents or procedures to enlarge intra-abdominal space are warranted for type II and III GIH. •Surgical management of bilateral giant inguinoscrotal hernia is challenging as reduction of hernia contents to abdominal cavity may lead to development of abdominal compartment syndrome (ACS) and cardiorespiratory complications.•We report a case of bilateral GIH managed with bilateral mesh repair with postoperative monitoring for features of ACS and cardiorespiratory complications.•There was no significant complication in the postoperative period and no recurrence in six month follow-up period. This case report has been reported in line with the SCARE Criteria 2A 68-year-old male, known case of bilateral inguinoscrotal hernia for 20 years presented to our center with complaint of increasing difficulty in micturition for past two years. He had multiple episodes of acute urinary retention that required catheterization. The patient couldn't walk and sit properly. The swelling had become irreducible with time. He didn't have abdominal pain, distension, and vomiting. He didn't have any co-morbidities.Physical examination revealed bilateral massive inguinoscrotal swelling that descended to just below midpoint of inner thigh in the standing position . There wPatient underwent elective exploration via inguinoscrotal approach in tertiary care hospital by a team of general and gastrointestinal surgeons and mesh hernioplasty performed on bilateral inguinal region. Intra-operatively, large hernia sac was present containing omentum and small bowel with only the proximal ileum A and B. A double-layered closure by prolene surgical mesh was done followed by reconstruction of the wall. This was followed by exploration of contralateral left inguinoscrotal hernia. Intraoperatively, we found hernia sac containing omentum and small bowel with only the proximal jejunum lying within the sac. Adhesiolysis was done and manual reduction of hernia content was done through the deep inguinal similar to left inguinal hernia. Closure was done with Prolene Mesh followed by reconstruction of wall and bilateral inguinal drain was placed .Fig. 3ClPostoperatively, there was early return of bowel movement and mobilization. His intraabdominal pressure was monitored routinely to avoid abdominal compartment syndrome. No respiratory complication was seen during his stay in hospital. On the seventh postoperative day, the drain was removed before discharge. Small postoperative inguinal seroma developed which resolved within few weeks without surgical intervention. There was no evidence of recurrence at six months during follow up.3Giant inguinoscrotal hernia (GIH) is defined as hernia extending below the midpoint of inner thigh of a patient in erect position In 2013, Akpo conducted a study focusing on psychosocial aspects of bilateral GIH. The patients visited medical facility either due to inability of penetration or denial of sexual intercourse by partners. They presented late because of financial constraint or neglect of the disease despite understanding that surgery is necessary for treatment. These patients also experience difficulty in movement like our patient and at times face acute complications like bowel obstruction and acute retention of urine. These consequences significantly impair their quality of life. Our patient also experienced multiple episodes of acute retention of urine which can possibly be due to constrictive effect of enlarged scrotum on buried penis. In the same study, Akpo also gave classification of bilateral GIH for the first time Considering the rarity of the disease and unavailability of standard approach, dilemma exists among healthcare providers for management of GIH Trakarnsagna A et al. classified GIH into three types on the basis of extent of hernia sac, based on which management principles differ. In type I GIH (hernia that extends between midpoint of inner thigh and the midpoint of the mid-inner thigh and suprapatellar margin), hernioplasty with forced reduction with post-operative intra-abdominal and intra-thoracic pressure monitoring is considered enough. However, in other types, resection of contents or increased intra-abdominal volume procedures is warranted to prevent intra-abdominal hypertension One study conducted among 32 patients with type I GIH including a case of bilateral GIH showed that laparoscopic surgery using Transabdominal Pre-peritoneal (TAPP) approach with negative pressure drain can be performed with safety and low post-operative complications In type II and type III GIH with loss of domain, additional procedures to prevent ACS should be considered. Various approaches used for prevention are resection of hernia contents and procedures to enlarge intra-abdominal volume The techniques mentioned earlier are either used alone or in combination for GIH  as mentioned in some recent studies Despite emergency surgical intervention, a rare case of fatality in bilateral GIH has been reported in an obese patient presenting with respiratory distress 4Type I GIH, including bilateral GIH, can be treated safely with simple hernioplasty. However, patient should be monitored vigilantly for features of ACS and respiratory complications during the postoperative period. In type II and type III GIH, additional measures like resection of hernia contents or procedures to enlarge intra-abdominal space are required.The case report is exempt from ethical approval in our institution.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Sunil Basukala (SB), Sabina Rijal (SR), Narayan Thapa (NT), Rakesh Kumar Gupta (RKG) = Study concept, Data collection, and surgical therapy for the patientSB, SR, Bishnu Deep Pathak (BDP) = Writing - original draft preparationRM, SR, BDP = Editing and writingNT and RKG = senior author and manuscript reviewer.All the authors read and approved the final manuscript.Sunil Basukala.Not applicable.Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.Not commissioned, externally peer-reviewed.None.


Previous research suggests depressive symptoms and loneliness are increasingly prevalent among older adults living in lower-income neighborhoods. The purpose of this study was to examine the extent to which neighborhood socioeconomic status (SES) was associated with depressive symptoms and loneliness among a sample of older adults from the Healthy Heart and Mind Study ; 66.7% women; 40.6% African American). It was hypothesized that older adults living in neighborhoods with greater socioeconomic disadvantage would report more depressive symptoms and loneliness than those residing in neighborhoods with less socioeconomic disadvantage. Depression was assessed with the Beck Depression Inventory-II (BDI-II), and loneliness was assessed using the Revised University of California, Los Angeles (UCLA) Loneliness scale. Neighborhood SES was measured with the Area Deprivation Index (ADI), which allows rankings of neighborhoods by SES disadvantage both statewide and nationally. After controlling for demographic variables , linear regression analyses showed that greater neighborhood SES disadvantage was associated with higher depression scores  and higher loneliness scores . These findings highlight the importance of neighborhood context on mental health in older adults, as underserved populations are more likely to experience declines in mental health under strenuous circumstances. Future research should investigate the impact of neighborhood SES on mental health in aging adults.


Aging elicits dramatic changes to DNA methylation (DNAm), however the causes and consequences of such alterations to the epigenome remain unclear. The utility of biomarkers of aging based on DNAm patterns would be greatly enhanced if in vitro models existed that recapitulated physiological phenotypes such that modulation could garnish mechanistic insights. Using DNAm from serially passaged mouse embryonic fibroblasts, we developed a marker of culture aging and asked if culture phenotypes, like exhaustive replication, are epigenetically analogous to physiological aging. Our measure, termed DNAmCULTURE, accurately estimated passage number and was shown to strongly increase with age when examined in multiple tissues. Furthermore, we observed epigenetic alterations indicative of early cultured cells in animals undergoing caloric restriction and in lung and kidney fibroblasts re-programmed to iPSCs. This study identifies culture-derived alterations to the methylome as physiologically relevant and implicates culture aging as an important feature in known epigenetic aging phenomena.


Researchers worldwide are repeatedly warning us against future zoonotic diseases resulting from humankind’s insurgence into natural ecosystems. The same zoonotic pathogens that cause severe infections in a human host frequently fail to produce any disease outcome in their natural hosts. What precise features of the immune system enable natural reservoirs to carry these pathogens so efficiently? To understand these effects, we highlight the importance of tracing the evolutionary basis of pathogen tolerance in reservoir hosts, while drawing implications from their diverse physiological and life-history traits, and ecological contexts of host-pathogen interactions. Long-term co-evolution might allow reservoir hosts to modulate immunity and evolve tolerance to zoonotic pathogens, increasing their circulation and infectious period. Such processes can also create a genetically diverse pathogen pool by allowing more mutations and genetic exchanges between circulating strains, thereby harboring rare alive-on-arrival variants with extended infectivity to new hosts . Finally, we end by underscoring the indispensability of a large multidisciplinary empirical framework to explore the proposed link between evolved tolerance, pathogen prevalence, and spillover in the wild. Plasmodium knowlesi (Rattus norvegicus) and domestic  species that are known to share more zoonotic pathogens with humans than other animal taxa  can remain infected with the Marburg virus for 7 months after inoculation , a small number of individuals can shed Brucella abortus, the causative agent of brucellosis, persistently at a high level for more than 2 months . Growing evidence suggests that besides causing severe flu-like symptoms in humans , host-pathogen interactions have been traditionally viewed as purely antagonistic. Consequently, studies on pathogen defense have primarily focused on mechanisms that host typically use to resist infections by activating immune responses . This biIn this review, we are primarily addressing how disease tolerance in reservoir species can be intrinsically linked to the maintenance and transmission of pathogens and their spillover. We first discuss why and how tolerance might naturally evolve during long-term association between natural hosts and pathogens as an effective strategy. We then outline the favorable ecological and evolutionary contexts vis-à-vis host-pathogen tolerogenic interactions that may maximize the spillover risk  where individuals can harbor high viral titers without showing any significant morbidity, suggesting features of infection tolerance (Hemignathus virens) from low-elevation regions show a reduced rate of weight loss and better physiological condition even during the acute-phase infection with Plasmodium relictum than their high-elevation counterparts, indicating their higher tolerance to pathological effects of avian malaria (Microtus agrestis), mature males can maintain better body condition than immature males while harboring very high macro- and micro-parasite loads, again indicating a higher tolerance (Bufo americanus) and green frogs (Rana clamitans) also show characteristics of relatively higher tolerance to Echinostoma trivolvis, a locally abundant trematode species, compared to younger tadpoles , the natural reservoirs for the Marburg virus, lack the induction of several pro-inflammatory genes that are classically implicated in primate filoviral pathogenesis such as CCL8, FAS, and IL6  and African green monkeys (Chlorocebus aethiops) infected with SIV show acute early inflammation, but they also possess regulatory mechanisms to rapidly control such responses; for example, they use anti-inflammatory inhibitory cytokines such as transforming growth factor-β (TGF-β) and IL-10  infected with Sin Nombre virus (SNV) also upregulate cytokines that correspond to Treg responses, prolonging the viral presence (R. norvegicus) infected with Seoul virus (SEOV) not only reduce the pro-inflammatory mediators such as interleukin-6 (IL-6) or TNF-α in their lungs but also increase the expression of regulatory factors TGF-β  proliferation, tolerating the effects of viral infection  populations performed by Hayward and coworkers  from two locations with a different coevolutionary history of infection by bacterium Mycoplasma gallisepticum was particularly helpful here  and higher levels of anti-inflammatory cytokine (IL-10)  isolated from regions with longer exposure to heartworm (Dirofilaria immitis) also showed higher tolerance compared to populations with little exposure to the parasite  . In anotparasite . These rparasite . In rode strongly supports this possibility where small isolated populations had a higher abundance of henipaviruses and extended within-host latency  and chikungunya  virus (CHIKV)  possibly derived from a bat-isolated orthoreovirus (Perameles bougainville), which exhibited genomic properties of both the Papillomaviridae and the Polyomaviridae family of viruses (Rousettus leschenaultii bats for 2 years found recombinants of RdRp (RNA-dependent RNA polymerase) and p10 genes in Ro-BatCoV GCCDC1 within as early as 5 months since the initial surveillance began  and SIV (retrovirus) might persist together in their natural hosts sooty mangabeys , which s (CHIKV) . Althoug (CHIKV) . For exa (CHIKV) . This is (CHIKV) . Also, ireovirus . In thisreovirus . Another viruses . These oce began .Pathogens, especially viruses, can evolve much faster than their hosts, presenting numerous mechanisms to avoid immune sensing . SIV, foConversely, host-pathogen tolerogenic interactions over an evolutionary timescale might also lead to progressive loss of immune evasion mechanisms in the pathogen, potentially reducing their infectivity to future hosts. Perhaps, one of the best-documented examples includes Myxoma virus (MYXV), which is highly pathogenic to European rabbits, with a case fatality rate close to 100% . The samFinally, recent vaccination studies in poultry birds can also offer some important clues on how tolerance can in principle influence the pathogen persistence and diversity. This is particularly true for vaccines that operate by reducing the disease symptoms , rather than preventing the infection, pathogen replication, and transmission . InfectiAnother example is live vaccination with attenuated strains of porcine reproductive and respiratory syndrome virus (PRRSV), which prevents the development of disease symptoms in pigs but does not protect them against contracting the infection . In factHost immune strategies, ecology, and pathogen prevalence all play instrumental roles in facilitating spillover, but studying them in isolation is far from ideal given the complex interactions that are involved therein. Costly immune responses might evolve to act at suboptimal levels in the wild due to constraints from available resources and physiological states . AlthougOur understanding of emerging diseases from natural reservoirs has increased substantially over the past two decades , but unfTransmission dynamics might also be contingent on intermediate hosts and vector populations . UnderstLong-term tracking of pathogens and disease with altered species interactions is perhaps most relevant for rapid land-use changes in recent decades  – deforehttps://www.globalviromeproject.org; https://ibol.org/programs/bioscan), the extension of the International Barcode of Life Program . Finally, proactive programs aimed at pandemic prevention also critically need more spatial and temporal information describing key changes in ecological communities  and environmental parameters  to better understand why circulation and transmission risk of zoonotic pathogens might vary across ecosystems. A recent web-based application ‘SpillOver’ is particularly useful to gain some of these insights , was operational until recently to identify broad patterns of emerging pathogens with pandemic potential in geographical regions that are disease hotspots such as the Republic of Congo, China, Egypt, India, and Malaysia . However Program , and theinsights . In addiAn integrated program to catalog pathogens across species, populations, and locations will prepare a unique stage to subsequently ask more mechanistic questions; for example, explaining the macro-scale structural variations, using diverse metrics of host immunological, ecological, and physiological parameters. However, multiple challenges need to be overcome to conduct any meaningful analyses. Below, we describe the indispensability of accepting the challenges and testing the natural variation in immune strategies and their complex interplay with life-history to explain EID prevalence and emergence.Batrachochytrium salamandrivorans that usually infects amphibian skins  as a proxy in a wild population of cyprinid freshwater fish  , tolerance was quantified by assessing eye cataract formation as a degree of pathology against increasing burden of eye fluke Diplostomum pseudospathaceum (Ovis aries) populations to distinguish how natural selection acts separately on three functionally distinct isotypes of antibodies  against a prevalent nematode parasite Teladorsagia circumcincta  . In Atlaathaceum . All theumcincta . Future Anolis sagrei lizards also used body condition, locomotor performance, and survival to the end of the breeding season as a function of infection with Plasmodium parasites  feeding on a low protein diet showed increased tolerance to Photorhabdus luminescens , however, found increased tolerance to skin penetrating nematode Aplectana sp. when maintained on proteinaceous insect diets  found multiple such highly polymorphic sites in the receptor regions, which interacts with the spike proteins of a coronavirus isolated from the same species of bats named as SARSr-CoV  rapidly evolved to antagonize host restriction factor tetherin by acquiring mutations in the accessory protein Vpu within merely four passages through an atypical HIV-1 host species pigtailed macaques  can help us to partially overcome the uncertainties associated with quantifying parasite burden and estimating fitness traits in the wild .Yet it might be challenging to answer some of the most fundamental questions, such as do hosts actually evolve tolerance to their natural pathogens? If so, how do we track such evolutionary processes? Besides gathering clues from comparative studies using various host populations, laboratory experimental evolution using tractable animal models (with known biology and genomic information) can be an excellent alternative to test these possibilities . They caArmigeres subalbatus is a natural vector for the zoonotic filarial worm Brugia pahangi whom they can tolerate, but not the morphologically and biologically similar pathogen Brugia malayi , which is crucial for their tolerance and survival against chikungunya virus and dengue virus, respectively (Aedes populations lacking (or with inherently lower) viral tolerance; (2) impose long-term viral selection to directly test whether stronger tolerance is correlated with increased vDNA synthesis; and (3) finally, test whether such evolved tolerance can be reversed by reducing vDNA synthesis (using reverse genetics) to verify its functional role  and the dynamics of noninfectious diseases (e.g., increased risk autoimmune disorders in geographical regions where improved hygiene has reduced pathogen burden;


In the immediate postoperative period, cell-free hemoglobin (CFH) and lactate dehydrogenase (LDH) were significantly lower in the study group than in the control group . Moreover, patients treated with the magnetic levitation pump showed lower creatinine and indirect bilirubin  [Increased plasma concentrations of circulating cell-free hemoglobin (CFH) are supposed to contribute to the multifactorial etiology of acute kidney injury (AKI). In their recent article: “The role of cell-free hemoglobin and haptoglobin in acute kidney injury in critically ill adults with ARDS and therapy with VV ECMO.”, Graw et al. identified a cohort of 1044 ARDS patients with CFH and haptoglobin measurements before initiation of ECMO therapy. They concluded that in critically ill patients with ARDS requiring therapy with VV ECMO, increased plasma concentration of CFH were an independent risk factor for AKI. Among patients with increased CFH concentrations, higher plasma haptoglobin concentrations might protect from CFH-associated AKI [


During the publication process of the original article  an errorUn Jung KangThe correct corresponding authors are:Luis Concha-Marambio, Roland G. Heym, Claudio Soto, Byron Caughey and Un Jung KangThe incorrect corresponding author was:The publisher apologizes for the inconvenience caused to the authors and readers.


Standard treatment of Parkinson’s disease involves the dopaminergic medications. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an important neurosurgical intervention often used as alternative treatment to drug therapy; however, it can be associated with increase of impulsive behaviors. This descriptive review focused on studies investigating the correlation between Deep brain stimulation of the subthalamic nucleus and impulsivity in Parkinson’s disease patients, arguing, the action’s mechanism and the specific role of the subthalamic nucleus. We searched on PubMed and Web of Science databases and screening references of included studies and review articles for additional citations. From initial 106 studies, only 15 met the search criteria. Parkinson’s Disease patients with and without Deep Brain Stimulation were compared with healthy controls, through 16 different tasks that assessed some aspects of impulsivity. Both Deep brain stimulation of the subthalamic nucleus and medication were associated with impulsive behavior and influenced decision-making processes. Moreover, findings demonstrated that: Impulse Control Disorders (ICDs) occurred soon after surgery, while, in pharmacological treatment, they appeared mainly after the initiation of treatment or the increase in dosage, especially with dopamine agonists. The subthalamic nucleus plays a part in the fronto-striato-thalamic-cortical loops mediating motor, cognitive, and emotional functions: this could explain the role of the Deep Brain Stimulation in behavior modulation in Parkinson’s Disease patients. Indeed, increase impulsivity has been reported also after deep brain stimulation of the subthalamic nucleus independently by dopaminergic medication status. Deep brain stimulation of the sub-thalamic nucleus (STN-DBS) is an important neurosurgical intervention that could determine, as well as dopaminergic medication, relevant side effects such as increased impulsivity.The studies analyzed in this review showed that after the surgical intervention, impulsivity improves independently by dopamination medication status. These findings could help to individuate contrasting data about the role of DBS on impulsivity in PD patients.Future research should include the study of other factors, such as genetic predisposing, direct effect on limbic part of STN, cognitive outcome or depression scores, and should conduct larger, prospective, controlled trials to better clarify how different subcomponents of impulsivity can be modulated both by dopaminergic drugs and STN-DBS.decisional forms, including delay discounting ;reduced sensitivity to adverse outcomes (negative prediction errors) during learning;reflection impulsivity (rapid decision-making);risk-taking and response conflict (slowing and errors with competing responses);motor forms, such as response inhibition  .Parkinson’s disease (PD) is a neurodegenerative disorder due to loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) and it is characterized by tremor, rigidity, and bradykinesia . AlthougDeep brain stimulation (DBS) is an adjunctive therapy to reduce some of the symptoms of an advanced stage that responds to levodopa Deep brain stimulation (DBS) is an adjunctive therapy in reducing some of the symptoms of advanced, levodopa-responsive. It improves motor disability by 33%—67%, motor fluctuations by 73%—83%, and dyskinesias caused by levodopa –15. DBS This descriptive review focuses on the studies that investigated the effect of STN-DBS on impulsivity in PD patients and argued its possible mechanisms of action.The sample population included PD patients with STN DBS;Studies provided a neuropsychological assessment of impulsivity and neurocognitive performances;Data compared the performance of PD patients on/off stimulation and on/off medication and healthy controls (HC);We excluded studies on PD patient with dementia or affected by other neurological or major psychiatric disorders;Animal studies and published in non-peer reviewed research were excluded;We excluded case studies.Studies were identified in PubMed  and Web of Science databases (November 2007 — January 2020). The search combined the following terms: ("impulsive behavior" [MeSH Terms] OR ("impulsive" [All Fields] AND "behavior" [All Fields]) OR "impulsive behavior" [All Fields] OR "impulsive" [All Fields]) AND ("deep brain stimulation" [MeSH Terms] OR ("deep" [All Fields] AND "brain" [All Fields] AND "stimulation" [All Fields]) OR "deep brain stimulation" [All Fields]) AND ("parkinson disease" [MeSH Terms] OR ("parkinson" [All Fields] AND "disease" [All Fields]) OR "parkinson disease" [All Fields] OR "parkinsons" [All Fields]). The search terms were identified in the title and abstract. We selected only English texts. After duplicates had been removed, articles were evaluated based on the title, abstract, and text. Studies that examined impulsivity in PD patients were included, after they fulfilled the following criteria:Of 108 studies identified, 15 met the inclusion criteria  task , 28 and Reference  examinedThe effects of DBS on impulsivity were also investigated by other tasks involving inhibitory control or response selection under conflict. In Simon task, that produced conflict from response impulses in patients with PD and HC, responses were faster and more accurate when relevant (color) and irrelevant  features of an imperative stimulus corresponded to the same response, but slower and less accurate when these features signaled conflicting responses . STN-DBSSince it is not yet clear what aspects of PD are actually caused by Basal Ganglia (BG) dysfunction,  investigStimulation of the ventromedial STN through its close connection to the nucleus accumbens loop potentially induces ICD . These cSTN plays a key role in inhibition processes, which permit the suppression of premature actions and to block interference from irrelevant stimuli. Altered decision-making is associated with cognitive impulsivity, which is considered the inability to weigh the consequences of immediate and future events and, consequently, delay gratification . Lesion Two studies hypothesized that STN DBS selectively improves inhibitory functions , 41. ThiStudies on impulsivity in PD patients highlighted conflicting results. DA seems to represent the main risk factor that leads to “reflection impulsivity”. Indeed, ICDs predominantly occurred subsequent to treatment initiation or dosage increase particularly related to the effects of the DA , 25. HowContrasting data suggest that STN-DBS significantly improves the proficiency of reactive inhibitory control , 41 and The etiology and pathogenesis of treatment-induced impulsivity in PD remain unknown , though


While spinal interbody cage options have proliferated in the past decade, relatively little work has been done to explore the comparative potential of biomaterial technologies in promoting stable fusion. Innovations such as micro-etching and nano-architectural designs have shown purported benefits in in vitro studies, but lack clinical data describing their optimal implementation. Here, we critically assess the pre-clinical data supportive of various commercially available interbody cage biomaterial, topographical, and structural designs. We describe in detail the osteointegrative and osteoconductive benefits conferred by these modifications with a focus on polyetheretherketone (PEEK) and titanium (Ti) interbody implants. Further, we describe the rationale and design for two randomized controlled trials, which aim to address the paucity of clinical data available by comparing interbody fusion outcomes between either PEEK or activated Ti lumbar interbody cages. Utilizing dual-energy computed tomography (DECT), these studies will evaluate the relative implant-bone integration and fusion rates achieved by either micro-etched Ti or standard PEEK interbody devices. Taken together, greater understanding of the relative osseointegration profile at the implant–bone interface of cages with distinct topographies will be crucial in guiding the rational design of further studies and innovations. Solid bony fusion is an essential requirement for successful spinal arthrodesis surgery that allows for stability of adjacent vertebrae –4. A comEnhancements to implant topography and architecture, including surface treatments and porous technologies, can putatively accelerate osseointegration and osteoconduction, which is key to long-term biomechanical function of interbody devices , 14, 15.The purpose of this article is to critically assess the tissue engineering potential of modified implant surfaces in spinal surgery, in particular with respect to the ability of activated surface and scaffold designs to accelerate or enhance osseointegration and structural stability following spinal instrumented arthrodesis procedures. We review a new imaging modality, dual-energy computed tomography (DECT), which allows for additional image post-processing and material characterization not possible with conventional systems. Finally, we discuss the rationale for two recently initiated randomized clinical trials designed to evaluate the rate of early osseous fusion using DECT within either activated Ti or PEEK lumbar interbody cages. Taken together, we believe that new insights will soon be gained to help elucidate the potential relative efficacy of microscopic lattice structures in accelerating the process of osseointegration and fusion.While current lumbar interbody cage designs are generally associated with favorable radiologic and clinical outcomes –23, fullA recent in vitro evaluation showed that implants bearing a trabecular scaffolded topography enhance cellular proliferation, bone matrix formation, and mineralization with increased mechanical strength by 20% for compression strength and 60% for compressive modulus . FurtherOne critical implant property that can play a role in osteoconduction and osseointegration is the three-dimensional geometry and intricately designed porosity. Specifically, interbody cage porosity accommodates bone ingrowth with the potential to yield improved implant fixation , 31. A mImplant surface roughness and surface finish also may play a significant role in promoting osseointegration . An earlAnother study compared osseointegration when alumina and a multiphase calcium phosphate (MCD) were used as the blast media. Blasted Ti alloy (Ti6Al4V) cylinders were implanted into rabbit tibiae and then evaluated two and four weeks after implantation. The histologic results showed the MCD to elicit significantly greater volume of new bone formation . A more Intriguingly, the combination of nanostructures onto microroughened surfaces may synergistically enhance the production of osteoblast differentiation markers and local factors important for bone formation compared to unmodified microrough controls . Indeed,Yet another factor that can influence the biomimetic properties of the bone–implant interface is the modulus of elasticity. Specifically, 3DP can design implants with an elasticity modulus resembling natural or cadaveric tissue. As a result, a better elastic recovery, biodegradability and cytocompatibility is expected , 46. MorA number of activated Ti cages are commercially available but with no long-term clinical evidence supporting their relative efficacy in promoting early osseointegration and fusion , 49. A r® or Trial 2: straight-shaped Medtronic AdaptixTM) versus PEEK cages.Clinical confirmation of enhanced osseointegration or bony fusion through activated Ti cages remains lacking. As such, the principal author (HFF) has designed two separate randomized double-arm single-blinded studies in patients undergoing either single- or double-level instrumented arthrodesis procedures  to compare radiologic and clinical outcomes using either activated Ti cages  implanted at each level of single- or contiguous double-level lumbar arthrodesis procedures. Both cages will be used in conjunction with milled local autograft bone generated as part of the spinal decompression portion of the procedure. Clinical and radiographic outcomes are being collected at regular intervals post-operatively. The primary outcome measure of effectiveness is radiographic bony fusion as assessed by an independent neuroradiologist at 6 months post-operatively, which grossly corresponds to the early phase of expected fusion following lumbar interbody cage placement. Radiographic bone fusion will be graded by the method of Brantigan and Steffee as modified to describe the Fraser definition of locked pseudoarthrosis  with a Grade BSF-3 being considered successful bone fusion. Grade BSF-3 is defined by radiographical fusion presenting bone bridges within at least half of the fusion area with at least the density originally achieved at surgery  Figs. –4 54–59–5954–59.With current X-ray tube technology, it is not possible to generate monochromatic spectra for scanning and greater artifact is expected with a polychromatic beam. As such, the potential for diminished artifact stems from the ability of VMIs to simulate what would be expected with a monochromatic X-ray beam. Furthermore, VMI images can be generated at a wide range of energies with unique advantages depending on the problem at hand and material of interest Fig. . By geneFinally, DECT scans can be used to generate basis material decomposition maps. While the feasibility depends on the specific material of interest and its physical properties, these maps can be used to estimate the distribution and concentration of certain materials, which is not possible using conventional CT imaging. One such example, virtual non-calcium maps, are used to demonstrate marrow edema , 68, 69.Enhanced implant-bone integration and fusion rates may have significant clinical benefits, particularly in more complicated clinical scenarios where fusion may be delayed, such as in osteoporosis, smokers, or with concomitant immunosuppressant use. The results of these two trials should provide relevant information regarding the relative efficacy of activated Ti surfaces  in accelerating the process of osseointegration and fusion. Novel insights in this regard are likely to be gained with DECT imaging, whose potential advantages include enhanced artifact reduction. Our conclusions should also assist in the design of further multicenter studies evaluating potential clinical benefits, either for similar degenerative conditions or for more complex reconstructions such as in adult spinal deformity.


COVID-related safety concerns mandated suspension of our ongoing trial testing the effects of movement and social engagement in older adults with early-stage dementia and their caregivers (dyads). Participant vulnerability and the requirement for group social interaction complicated intervention resumption. We present results from a successful pilot to rapidly and iteratively optimize study interventions for remote delivery targeting intervention mediators  based on participant feedback. Three-dyad groups  completed cycles of intervention via Zoom immediately followed by an interview with open-ended and quantitative feedback. Cycles were repeated until no new information was solicited, then repeated with new participants. Optimization revealed needs for technological support, more intensive movement, and social connection. Specifically, the inability to make eye contact, see others’ full body, and technology-associated timing asynchronies impeded social connection in the movement group. We will present practical tips for crafting remote group interventions for caregiver/person living with dementia dyads.


Voriconazole is a broad-spectrum triazole antifungal used to treat invasive fungal infections. It is commonly used prophylactically in immunocompromized patient cohorts, including transplant recipients. Diffuse periostitis is a very rare complication of chronic voriconazole use. It is associated with diffuse bone pain, elevated serum alkaline phosphatase and fluorine levels. Characteristic imaging findings include periosteal thickening with a dense, nodular, irregular and often bilateral pattern. We describe the case of a 71-year-old female who presented with multifocal bone pain six years following double lung transplantation. Her post transplantation course had been complicated by a life threatening episode of sepsis secondary to Scedosporium apiospermum, a rare invasive fungal infection following which lifelong prophylaxis with oral Voriconazole was commenced. We discuss the characteristic clinical and imaging manifestations of this rare condition. A 71-year-old female presented with diffuse bone pain involving the shoulders and multiple ribs. On examination there was slightly reduced strength in both upper extremities, full although painful range of motion in the shoulder joints and diffuse tenderness at both shoulders and over multiple left-sided ribs. Her history was significant for double lung transplantation for emphysema six years previously. The post-transplantation course was complicated by severe sepsis due to Scedosporium apiospermum, a rare invasive fungal infection, requiring critical care admission. The patient was subsequently commenced on oral voriconazole as prophylaxis to mitigate against further fungal infection.). A diagnosis of voriconazole-induced periostitis was made based on these characteristic imaging appearances, in combination with the patient's history. This was supported by a significantly elevated serum alkaline phosphatase value of 220 U/L , a characteristic laboratory finding in voriconazole induced periostitis.Radiographs of the chest and shoulders were obtained . ChangesThe patient was commenced on an analgesic regime which resulted in significant symptom improvement. The possibility of discontinuing voriconazole prophylaxis was considered, but ultimately the significant benefit in terms of mitigation against fungal infection was considered to outweigh symptoms which were now well-controlled and the patient continued on lifelong voriconazole.Immunosuppression post-transplantation increases patients susceptibility to infection, which may be life-threatening. Voriconazole is commonly used in both the treatment and prophylaxis of fungal infections in organ transplant recipients.Frequently reported side effects of voriconazole include nausea and vomiting, visual disturbances, rash, abnormal liver function tests, QT prolongation, headaches and hallucinations. In 2009 the first cases of voriconazole induced periostitis were reported in 5 lung transplant patients receiving long-term prophylactic treatment with voriconazole Voriconazole is a tri-fluorinated compound. Several studies have shown that this increased fluoride level may play a role in the mechanism of how voriconazole causes periostitis Characteristic imaging features of periostitis include periosteal thickening, with new bone formation which tends to be dense and irregular. This is generally bilateral but may be asymmetric. Nuclear medicine imaging techniques such as bone scintigraphy or single photon emission computed tomography (SPECT) demonstrate radiotracer uptake at affected sites. The differential diagnosis for periostitis is broad, including entities such as hypertrophic osteoarthropathy, hypervitaminosis A, venous stasis and infection. The patient's clinical history (as well as the distribution of periositis) are crucial to accurate diagnosis.Voriconazole induced periostitis typically resolves following medication discontinuation (or in some cases dose reduction) In summary, though uncommon, voriconazole-induced periostitis is an important diagnosis for radiologists to be aware of in the post-transplant or otherwise immunocompromized patient. Accurate diagnosis requires assimilation of the relevant imaging characteristics and patient history.Informed consent has been obtained for the publication of this case report.None.


This multicenter care innovation program wassupported by a Centers for Medicare & Medicaid Services (CMS) Health CareInnovations Award. It includes transitional care nurses (TCNs) and social workers (SWs)who staff the GEDI WISE level 1 GEDs and conduct geriatric assessments , engage in conversationsabout goals of care, and assist with care coordination.JAMA Network Open, Hwang et al3 measured the cost savings associated with TCN orSW evaluations at GEDI WISE sites. Using entropy balancing, they compared the totalMedicare costs for 30 and 60 days after the index ED visit among an intervention groupof fee-for-service Medicare beneficiaries who received a TCN or SW evaluation and acontrol group of fee-for-service Medicare beneficiaries who did not. Whereas the priorGEDI WISE studies evaluated the association of this care model with ED visits andhospital admission rates, in this study Hwang et al3 conducted a more comprehensive evaluation of costs of care bylooking at total Medicare costs—including inpatient, outpatient, home health,hospice, and skilled nursing facilities claims. In doing so, they not only quantifiedthe cost savings related to avoidance of hospitalization and ED revisits but alsodetermined whether the cost savings were offset by increased care costs related to homehealth referrals or transfer to skilled nursing or acute rehabilitation facilities.Hwang et al3 found that after entropybalancing, patients who received the TCN or SW intervention had a mean 30-day savings of$2436 per beneficiary at 1 site and $2905 per beneficiary at the other site. The costsavings persisted at 60 days, with a mean savings of $1200 at 1 site and $3202 at thesecond site.Elsewhere in This study provides important evidence demonstrating the cost efficiency of thisenhanced care model for geriatric emergency care. Evidence that higher-quality models ofcare, such as GEDs, can reduce health care costs should catalyze the adoption of thesemodels. This is more likely to happen when the savings generated benefit the entityshouldering the costs. However, in the GEDI WISE program, the savings went to the payer,in this case Medicare, while the costs of sustaining this intervention beyond thegrant-funded period were borne by the hospitals. Asking hospitals to spend their ownmoney to save Medicare money is unlikely to be sustainable. Growth of this care modelrequires that health care systems also benefit financially from the cost savings.6 In these advanced ACO reimbursement models, theorganization receives additional revenue when savings are generated and quality of careis maintained or improved. Another mechanism for funding advanced geriatric emergencycare models is through collaboration with Medicare Advantage plans, given that theseplans benefit from reducing costs while improving quality of care. Health care systemsshould collaborate with ACOs and/or their local Medicare Advantage plans whenimplementing a GED model of care because these parties all stand to benefit from thesavings demonstrated in this study.The traditional way Medicare has incentivized individual clinicans, hospitals,and health care systems to adopt new services is to directly pay for it—allowingclinicians and health care systems to submit bills for the services they have provided.While this is a mechanism that could be used to reimburse facilities for a TCN or SWconsultation or a similar GED care model, creating new billing codes is an arduous andprolonged process and not likely to create additional revenue for GEDs anytime soon. CMSis encouraging the adoption of value-based care models in which organizations  financially benefit from providing high-value care.CMS is accomplishing this by encouraging organizations to take on financial risk formanaging patient populations in risk-sharing Accountable Care Organization (ACO) models.These models hold organizations responsible for financial risk if they provide low-value care to their patient populations.7 Wemust consider how geriatric care models developed in large academic EDs in metropolitanareas can be disseminated to small EDs in rural locales. Telehealth is an obviousanswer. Through a telehealth platform, a single TCN or SW could conduct consultationsacross multiple EDs, improving efficiency and expanding access to this care model.Home-based care alternatives are another option that is cost saving for payersand revenue generating for hospitals. Instead of admitting an older adult with complexcare needs to the hospital, a GED could admit that patient to a hospital-at-home programor leverage telehealth and/or remote monitoring programs for follow-up. Telehealth mayalso be a viable solution for disseminating GED models of care across the United States.While the GEDI WISE sites are level 1 GEDs in large metropolitan areas, at least 18% ofolder adults reside in rural areas.The next phase of research into models for geriatric emergency care must examinethe association of GEDs with carefully selected, patient-centered outcomes that mattermost to older adults. This research may include evaluation of GED care models onphysical functioning, cognition, and quality of life. For instance, does avoidance ofhospitalization through the GED model of care result in improved physical activity andprevent functional decline? Will GED models of care prevent delirium in older adultswith acute medical care needs? Do GED initiatives improve quality of life in olderadults requiring emergency care? Quality of life is a measure that encompasses anindividual’s physical, mental, emotional, and social functioning and could serveas a composite patient-oriented outcome in future studies evaluating the consequences ofgeriatric emergency care innovations.Now that the cost savings of enhanced geriatric emergency care are clear, we needto consider how we can leverage payer models to increase adoption of these programs anddisseminate them to nonmetropolitan areas. We also need to conduct robust research toevaluate the association of GEDs with outcomes among older adults using apatient-centered approach and focusing on what matters most to this population. Throughthis framework, we can increase access to high-quality, cost-effective,geriatric-centric emergency care in the United States for older adults.


The development of antimicrobial drug resistance has encouraged scientists to develop alternate methods to combat infectious pathogens associated with dental diseases. Therefore, it is of interest to predict interactions for catechin (a plant derivedcompound) with protein targets in the red complex pathogens using computer aided network tools. However, in vitro and in vivo studies are warranted to confirm the antimicrobial effect of catechin  andgallolyl catechins) on the dental pathogens. Drug resistance to pathogens has reached alarming numbers in recent times. A global burden of antibiotic resistant organisms in the community as well as hospital settings is seen due to indiscriminate use of antibiotics. Oral micro flora is a complexenvironment wherein there is interplay between host and pathogens causing infectious diseases. Several pathogens of the oral cavity such as Enterococcus faecalis, Streptococcus mutans etc. are known to contain proteins responsible for drug resistant phenotypes,2. SelecThe mechanism underlying the anti-microbial activity of catechin against red complex pathogens is investigated using available computer aided predictive tools.The strains of red complex pathogens sich as Porphyromonas gingivalis ATCC 33277, Treponema denticola ATCC 35405 and Tannerella forsythia ATCC 43037 available in the STITCH database were selected for the analysis  virulence factors; (2) information and storage processing; (3) cellular process and (4) metabolism. The virulence factors are identified using a support vector machine (SVM)algorithm, which classifies proteins based on their amino acid composition and sequence pattern .VirulentPred is a yet another SVM based method, used for automated prediction of virulent proteins based on the sequences . The scoCatechin is a major component of green tea known for its antioxidant, anti-inflammatory, anti-proliferative activities. Bai et al. has shown the antimicrobial activity of catechin against a canine dental pathogen . Itis oWe document the predicted interaction targets for catechin (a plant derived compound) with protein targets in the red complex pathogens using computer aided network tools. However, in vitro and in vivo studies are necessary to verify the antimicrobial effectof catechin  and gallolyl catechins) on the dental pathogens.


Targeted anti-cancer therapies have revolutionised melanoma patient care; however, cures remain uncommon due to acquired drug resistance that results in disease relapse. Recent insights from the clinic and experimental settings have identified a key role for metabolic plasticity, defined as the flexibility to utilise different nutrients and process them in different ways, in both disease progression and response to targeted therapies. Here, we discuss how this plasticity creates a moving target with important implications for identifying new combination therapies.Resistance to therapy continues to be a barrier to curative treatments in melanoma. Recent insights from the clinic and experimental settings have highlighted a range of non-genetic adaptive mechanisms that contribute to therapy resistance and disease relapse, including transcriptional, post-transcriptional and metabolic reprogramming. A growing body of evidence highlights the inherent plasticity of melanoma metabolism, evidenced by reversible metabolome alterations and flexibility in fuel usage that occur during metastasis and response to anti-cancer therapies. Here, we discuss how the inherent metabolic plasticity of melanoma cells facilitates both disease progression and acquisition of anti-cancer therapy resistance. In particular, we discuss in detail the different metabolic changes that occur during the three major phases of the targeted therapy response—the early response, drug tolerance and acquired resistance. We also discuss how non-genetic programs, including transcription and translation, control this process. The prevalence and diverse array of these non-genetic resistance mechanisms poses a new challenge to the field that requires innovative strategies to monitor and counteract these adaptive processes in the quest to prevent therapy resistance. Cancer cells must continuously reprogram their metabolism in order to maintain proliferation and survival in response to changes in the surrounding microenvironment. Metabolic reprogramming in cancer is therefore rarely static but instead a highly dynamic process that allows rapid adaptability. This demand for metabolic adaptability requires both the flexibility to utilise different metabolic substrates and the ability to process metabolic substrates in different ways . CollectMetastasis is the leading cause of all cancer-related deaths and involves the elaborate reprogramming of many distinct cellular processes that allows cellular extravasation and invasive dissemination, circulation, and subsequent colonisation of distant tissues by cancer cells . The metThe first clear evidence of metabolic plasticity in melanoma metastasis comes from an elegant study by Piskounova and colleagues using melanoma patient-derived xenotransplant (PDX) models . Using aFurther evidence supporting a role for metabolic plasticity during melanoma progression and metastasis comes from a study investigating the role of peroxisome proliferator-activated receptor γ coactivator α (PGC1α), a master regulator of mitochondrial function . During Metabolic plasticity has also been linked with the development of site-specific melanoma metastases. Analysis of a large melanoma patient cohort identified significant upregulation of OXPHOS specifically in brain metastases when compared to patient matched extracranial metastases  Figure A. AnalysReprogrammed fatty acid metabolism has also been extensively linked with melanoma progression and metastasis . FurtherFlexibility in fuel usage has also emerged as a major factor that can facilitate melanoma metastasis. Melanoma cells of varying oncogenic backgrounds display highly glycolytic phenotypes in which 60–80% of glucose is converted to lactate, and this activity is enhanced to 90% or more in hypoxia . Using iThere is also clinical and experimental evidence supporting a role for alterations in lipid uptake in melanoma progression and metastasis. Analysis of melanoma patients in The Cancer Genome Atlas (TCGA) identified a gene signature that includes fatty acid uptake genes caveolin-1 (CAV1) and cluster of differentiation 36 (CD36), and the fatty acid oxidation (FAO) gene carnitine palmitoyltransferase 1C (CPT1C), that predicts for significantly worse overall survival . A clearOverall, these studies highlight the inherent plasticity of melanoma metabolism and how this can directly promote metastatic progression of disease. Importantly, these data also highlight that these events can occur independently from acquisition of new genetic events, indicated by the reversible nature of metabolome alterations observed in metastatic cells derived from different tissue origins. They also reveal the diversity of fuel sources melanoma cells can utilise to survive in different microenvironmental niches, another key feature of plasticity. As such, this inherent metabolic plasticity creates a moving target for therapeutic interventions and consequently poses a major challenge to effective therapy. Indeed, metabolic plasticity has emerged as a key feature of adaptive response and resistance to current standard-of-care oncogene targeted therapies for melanoma, and this aspect of metabolic plasticity in melanoma is discussed in detail below.V600 melanoma patients, and the Food and Drug Administration (FDA) has approved three combination therapies; dabrafenib/trametinib, vemurafenib/cobimetinib and encorafenib/binimetinib. Exceptional response rates and low toxicities are two major advantages of these targeted therapies over other anti-cancer therapies currently available in melanoma. However, despite their success in improving overall survival, persistence of a residual disease that eventually acquires resistance and drives disease relapse is a major barrier to achieving cures. Indeed, the dabrafenib plus trametinib combination in BRAF mutant melanoma patients has a 34% 5-year overall survival rate [Activating mutations in BRAF (V600) occur in approximately 40% of all melanoma patients and have led to the development of molecular targeted therapies directed against BRAF and mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK), two kinases in the mitogen-activated protein kinase pathway (MAPK) . BRAF anHistorically, genetic drivers of resistance to targeted therapies have been the major focus, and more than 20 genetic mechanisms of acquired resistance have been identified in melanoma so far . The preGlucose is a major fuel source for melanoma, and in general, melanoma cells display an elevated glycolytic phenotype at the expense of oxidative mitochondrial respiration ,50,51. IV600 also regulates the microphthalmia-associated transcription factor (MITF), a melanocyte lineage transcription factor, which is a crucial determinant of the response to BRAFi. Treatment with BRAFi leads to MITF dependent regulation of PGC1α, which subsequently promotes mitochondrial biogenesis, OXPHOS and response to oxidative stress in BRAFV600 melanoma cells  tRNA (U34 enzymes) are key players of rewired protein synthesis observed upon resistance to MAPK targeted therapy in melanoma [34 enzymes promote glycolysis through direct translational regulation of HIF1α mRNA that consequently maintains high levels of HIF1α protein to facilitate reactivated glycolytic networks in MAPKi resistant melanoma cells. Together, these data clearly show a role for glucose metabolism in acquired resistance, in addition to its role in the early MAPKi response.In addition to glucose consumption being a useful biomarker of the early targeted therapy response in melanoma (discussed above), reactivation of glucose uptake and glycolysis has also been observed upon acquisition of BRAF inhibitor resistance. Following early suppression of glucose consumption upon treatment with the BRAF inhibitor vemurafenib, subsequent increases in glucose uptake as assessed using FDG uptake in treated tumours tightly correlated with emergence of resistance . Consistsistance , restorent cells . Translamelanoma . MechaniFurther to glucose, increased dependence on glutamine has also been demonstrated in cells with acquired resistance to single agent BRAF inhibitors , and theThe ability to utilise alternative fuel sources such as glutamine and lipids is concordant with elevated mitochondrial biogenesis and oxidative metabolism signatures identified in MAPKi resistant melanoma patients ,58. IndeAltogether, these studies highlight a key role for metabolic plasticity across all major phases of the targeted therapy response and development of resistance in melanoma.The inherent plasticity of melanoma metabolism and the flexibility to use diverse fuel sources provides a survival advantage necessary to colonise harsh microenvironments and survive inhibition of metabolic pathways. Consequently, this creates a moving target for therapeutic interventions and poses a major challenge to effective therapy. While some activity with single agents has been observed in preclinical models, metabolic inhibitors will likely be most useful in combination with current anti-cancer targeted therapies. Indeed, targeting mitochondrial oxidative metabolism in melanoma has been shown to cause metabolic compensation through both glucose and glutamine utilisation in mouse models . MoreoveStrategies that target multiple metabolic pathways at the same time have shown some success. As discussed above, co-inhibition of mitochondrial metabolism with MAPKi, which effectively suppresses glycolysis, can improve the response and overcome acquired resistance to targeted therapies ,55,57,58Targeting metabolic features of drug tolerant cells that persist following treatment with anti-cancer therapies also represents a therapeutic opportunity to overcome acquired resistance and tumour relapse. Further characterisation of SMC populations that transiently emerge following exposure to therapy in melanoma tumours may therefore prove useful therapeutically. If the SMCs are precursors to other drug tolerant cellular states , then idAnother approach that warrants further investigation is targeting regulatory pathways underpinning plasticity in the metabolic network, and the available data suggests this occurs at the transcriptional and translational level. An extensive list of transcription factors has been directly linked with metabolic plasticity during melanoma metastasis and adaptive resistance to MAPKi . However, in general, therapeutically targeting transcription factors remains a challenge, and most efforts in melanoma have been directed at targeting downstream activated pathways (see above). Targeting translational mechanisms may offer an alternative approach, and multiple aspects of selective and global mechanisms of translational regulation are under investigation and have proven useful in preclinical settings. Silvestrol is a naturally occurring member of the flavagline family of compounds that inhibits cap-dependent translation by targeting eIF4A ; howeverA growing body of evidence now highlights the inherent plasticity of melanoma metabolism and how this can directly promote metastatic progression of disease and response to anti-cancer therapies. Importantly, adaptive metabolic reprogramming can occur independently from acquisition of new genetic events. This is indicated by the reversible nature of metabolome alterations observed in metastatic cells derived from different tissue origins and in melanoma cells that show transient and reversible activation of metabolic pathways as they acquire therapy tolerance and resistance. These studies also reveal the diversity of fuels melanoma cells can utilise to survive in different microenvironmental niches during both metastasis and response to anti-cancer therapies, which is another key feature underpinning metabolic plasticity. Targeting metabolic plasticity is therefore predicted to have therapeutic benefit in melanoma patients; however, the maximal benefit is likely to be achieved by combining therapies directed against metabolic plasticity with current anti-cancer therapies directed against MAPK signalling. Moreover, because plasticity creates a moving target for therapeutic interventions, an attractive approach would be to exploit the specific regulatory molecules that facilitate plasticity in the metabolome.


Thermal therapies such as radiofrequency ablation (RFA) are gaining widespread clinical adoption in the local treatment of skeletal metastases. RFA has been shown to successfully destroy tumor cells, yet the impact of RFA on the quality of the surrounding bone has not been well characterized. RFA treatment was performed on femora of rats with bone metastases (osteolytic and osteoblastic) and healthy age matched rats. Histopathology, second harmonic generation imaging and backscatter electron imaging were used to characterize changes in the structure, organic and mineral components of the bone after RFA. RFA treatment was shown to be effective in targeting tumor cells and promoting subsequent new bone formation without impacting the surrounding bone negatively. Mineralization profiles of metastatic models were significantly improved post-RFA treatment with respect to mineral content and homogeneity, suggesting a positive impact of RFA treatment on the quality of cancer involved bone. Evaluating the impact of RFA on bone quality is important in directing the growth of this minimally invasive therapeutic approach with respect to fracture risk assessment, patient selection, and multimodal treatment planning. Skeletal bone metastases occur in one third of all cancer  with freIn its use, a radiofrequency (RF) generator supplies an alternating current to a probe inserted into the tissue to be treated. Frictional heat induced by the electric current creates a thermal ablation zone. The RF circuit may be completed using grounding pads in unipolar designs  or with RFA leads to a coagulative necrosis within seconds to minutes and distinct defined tissue changes are visible after RFA dose delivery . TypicalArchitecture and tissue level material properties of bone impact its strength and are regulated through the mineral  and organic (primarily collagen) components of their ultrastructure –16. The In the organic component of bone tissue, the distribution and orientation of collagen type I fibrils are responsible for bone’s ductility and toughness . The recPrevious work by our group demonstrated different effects of various types of metastases on rat bone quality , 29–31. Foxn1rnu rats  through intracardiac injection under general inhalation anaesthesia. The intracardiac injection of luciferase transfected human ZR-75-1 (ATCC® CRL-1500™) breast cancer cells resulted in the development of osteoblastic metastases within 56 days. Intra-cardiac injection of 1.5 x 106 luciferase transfected HeLa cells . Th. Th38]. BMDD of healthy and metastatic bone is modified post-RFA. In healthy bone, regardless of the age of the model (Day 21 or Day 84), average mineral content is unchanged post-treatment. However, younger healthy bone (Day 21), demonstrates greater heterogeneity post treatment which may be due to the shorter recovery period. In the osteolytic bone metastases model, due to the aggressive nature of tumor growth, longer observation periods are not possible. In comparison to older healthy bone (Day 84), which is monitored for 28 days post-treatment and hence undergoes several remodeling cycles; age-matched younger healthy bone (Day 21) is only monitored for 7 days post-treatment  . SeveralPost-RFA treatment, osteoblastic bone tissue demonstrated an enhanced mineralization profile with improved homogeneity. Higher mineralization values (CaPeak) and elevated mineral content (CaMean) are observed post-RFA . It is eOur earlier work evaluating bone quality secondary to skeletal metastatic involvement has considered Raman spectroscopy in addition to SHG and BSE to assess changes in bone quality in pathologic vertebrae . In thisIn this study, the impact of RFA on the mineral and organic components of healthy and metastatic bone were assessed. In the context of skeletal metastases, RFA resulted in a more homogenous bone tissue by replacing the diseased bone with more mature, highly mineralized bone. RFA treatment was shown to be effective in targeting tumor cells and promoting subsequent new bone formation. RFA did not negatively impact healthy bone tissue. The positive impact of RFA on bone quality in metastatically involved bone is important in directing the utilization of this growing local minimally invasive therapeutic approach with respect to fracture risk assessment, patient selection and multimodal treatment planning.


Mobility, physical activity and social engagement are important to healthy aging and independent living among older adults. This symposium includes four related studies on these issues. Dr. Lien Quach and her team examined racial and ethnic disparities in social engagement among community-living older adults using data from the national Health and Retirement Study. The analysis found that Asians and Hispanics had significantly lower social engagement score compared with non-Hispanic Whites, advocating for further investigations of the causes of racial disparities in social engagement. Dr. Su-I Hou’s study examined the impact of physical activity and social relationship on social engagement. The study found positive impacts of more physical activity, better social relationships and volunteers on social engagement. The results have important implications to promotion of social engagement among older adults participating in aging-in-community programs. Dr. Ladda Thiamwong’s study demonstrated the benefits of using assistive health technology (AHT) to assess the relationships between fall risks, body compositions and objectively measured physical activity in older adults. Dr. Thiamwong’ will discuss the research protocol and preliminary results. Dr. Li’s Health Aging and Neighborhood Study examined variations of older adults’ driving behaviors by sex, age, race, income, health status and housing density of the neighborhoods. The study found substantial differences in mobility and driving patterns by both personal characteristics and neighborhood living environment. The findings have important implications to community programs that support older adults aging in place.


Although researchers have identified medications that relieve symptoms of Multiple Sclerosis (MS), none are entirely effective and some persons with multiple sclerosis (PwMS) use alternatives. Our study compared cannabis use among PwMS (N=135) and persons diagnosed with arthritis (N=582) or cancer (N=622) who participated in the Illinois medical cannabis program. We tested for significant differences across psychological well-being, quality of life and three behavioral outcomes, and also considered effects of co-occurring prescription opioid use. A majority of all individuals used cannabis to address pain and improve quality of sleep. PwMS reported lower levels of productivity, exercise and social activity, and cannabis was less helpful with improving these particular outcomes. Most persons used cannabis for sleep or digestive problems and we found no differences across groups in terms of well-being and quality of life. This comparative evaluation suggests cannabis mechanisms are not specific as much as they impact common processes.