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Abstract In the era of precision medicine, biopsies are playing an increasingly central role in cancer research and treatment paradigms; however, patient outcomes and analyses of biopsy quality, as well as impact on downstream clinical and research applications, remain underreported. Herein, we report biopsy safety and quality outcomes for percutaneous core biopsies of hepatocellular carcinoma (HCC) performed as part of a prospective clinical trial. Patients with a clinical diagnosis of HCC were enrolled in a prospective cohort study for the genetic, proteomic, and metabolomic profiling of HCC at two academic medical centers from April 2016 to July 2020. Under image guidance, 18G core biopsies were obtained using coaxial technique at the time of locoregional therapy. The primary outcome was biopsy quality, defined as tumor fraction in the core biopsy. 56 HCC lesions from 50 patients underwent 60 biopsy events with a median of 8 core biopsies per procedure (interquartile range, IQR, 7–10). Malignancy was identified in 45/56 (80.4%, 4 without pathology) biopsy events, including HCC (40/56, 71.4%) and cholangiocarcinoma (CCA) or combined HCC-CCA (5/56, 8.9%). Biopsy quality was highly variable with a median of 40% tumor in each biopsy core (IQR 10–75). Only 43/56 (76.8%) and 23/56 (41.1%) samples met quality thresholds for genomic or metabolomic/proteomic profiling, respectively, requiring expansion of the clinical trial. Overall and major complication rates were 5/60 (8.3%) and 3/60 (5.0%), respectively. Despite uniform biopsy protocol, biopsy quality varied widely with up to 59% of samples to be inadequate for intended purpose. This finding has important consequences for clinical trial design and highlights the need for quality control prior to applications in which the presence of benign cell types may substantially alter findings.

Cell-based mathematical models have previously been developed to simulate the immune system in response to pathogens. Mathematical modeling papers which study the human immune response to pathogens have predicted concentrations of a variety of cells, including activated and resting macrophages, plasma cells, and antibodies. This study aims to create a comprehensive mathematical model that can predict cytokine levels in response to a gram-positive bacterium, S. aureus by coupling previous models. To accomplish this, the cytokines Tumor Necrosis Factor Alpha (TNF-α), Interleukin 6 (IL-6), Interleukin 8 (IL-8), and Interleukin 10 (IL-10) are included to quantify the relationship between cytokine release from macrophages and the concentration of the pathogen, S. aureus, ex vivo. Partial differential equations (PDEs) are used to model cellular response and ordinary differential equations (ODEs) are used to model cytokine response, and interactions between both components produce a more robust and more complete systems-level understanding of immune activation. In the coupled cellular and cytokine model outlined in this paper, a low concentration of S. aureus is used to stimulate the measured cellular response and cytokine expression. Results show that our cellular activation and cytokine expression model characterizing septic conditions can predict ex vivo mechanisms in response to gram-negative and gram-positive bacteria. Our simulations provide new insights into how the human immune system responds to infections from different pathogens. Novel applications of these insights help in the development of more powerful tools and protocols in infection biology.

Pluchea indica is used in traditional medicine for the treatment of lumbago, ulcer, tuberculosis and inflammation. The anti-cancer activities and the underlying molecular mechanisms of the ethanolic extracts of P. indica root (PIRE) were characterized in the present study. PIRE strongly inhibited the viability of the human nasopharyngeal carcinoma cells (NPC-TW 01 and NPC-TW 04) in a time- and dose-dependent manner. Migration of cancer cells was also suppressed by PIRE. In addition, PIRE significantly increased the occurrence of the cells in sub-G1 phase and the extent of DNA fragmentation in a dose-dependent manner, which indicates that PIRE significantly increased apoptosis in NPC cells. The apoptotic process triggered by PIRE involved up-regulation of pro-apoptotic Bax protein and down-regulation of anti-apoptotic Bcl-2 protein, consequently increasing the ratios of Bax/Bcl-2 protein levels. Moreover, the p53 protein was up-regulated by PIRE in a concentration-dependent manner. Therefore, PIRE could induce the apoptosis-signaling pathway in NPC cells by activation of p53 and by regulation of apoptosis-related proteins.

Abstract The rising aging population underscores the need for advances in tissue engineering and regenerative medicine. Alterations in cellular response in microgravity might be pivotal in unraveling the intricate cellular mechanisms governing tissue and organ regeneration. Microgravity could improve multicellular spheroid, tissue, and organ formation. This review summarizes microgravity-induced cellular alterations and highlights the potential of tissue engineering in microgravity for future breakthroughs in space travel, transplantation, drug testing, and personalized medicine.

Abstract Background EM Talk is a communication skills training program designed to improve emergency providers’ serious illness conversational skills. Using the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework, this study aims to assess the reach of EM Talk and its effectiveness. Methods EM Talk consisted of one 4-h training session during which professional actors used role-plays and active learning to train providers to deliver serious/bad news, express empathy, explore patients’ goals, and formulate care plans. After the training, emergency providers filled out an optional post-intervention survey, which included course reflections. Using a multi-method analytical approach, we analyzed the reach of the intervention quantitatively and the effectiveness of the intervention qualitatively using conceptual content analysis of open-ended responses. Results A total of 879 out of 1,029 (85%) EM providers across 33 emergency departments completed the EM Talk training, with the training rate ranging from 63 to 100%. From the 326 reflections, we identified meaning units across the thematic domains of improved knowledge, attitude, and practice. The main subthemes across the three domains were the acquisition of Serious Illness (SI) communication skills, improved attitude toward engaging qualifying patients in SI conversations, and commitment to using these learned skills in clinical practice. Conclusion Our study showed the extensive reach and the effectiveness of the EM Talk training in improving SI conversation. EM Talk, therefore, can potentially improve emergency providers’ knowledge, attitude, and practice of SI communication skills. Trial registration Clinicaltrials.gov: NCT03424109; Registered on January 30, 2018.

Introduction: Older adults with cognitive impairment (CI) are more likely to visit the emergency department (ED) than those without CI. They are also more likely to suffer poor outcomes after an ED visit. Family and friends who serve as care partners contribute significant time and resources to the care of these patients and may need particular attention to their emotional needs during and after the ED encounter. In this study, we examined the association between patient and care partner characteristics on care partner depression and anxiety at the time of the ED visit. Methods: Baseline data from 640 patient-care partner dyads who were enrolled in a two-site randomized controlled trial at New York University Lagone Health and Indiana University. The goal of the trial was to evaluate a tailored collabotative care management program to reduce readmissions of ED patients older than 75 years with CI and reduce care partner burden. Eligible patients were ED patients aged ≥75 years with CI as measured by the Mini-Cog or the proxy-reported Short Informant Questionnaire on Cognitive Decline in the Elderly and a planned dicharge home. Eligble care partners were self-identified or identified by the patient. We collected patient and care partner demographics, care partner-reported patient medical and psychiatric history, daily needs of the patient, and patient-care partner relationship. We used descriptive statistics and logistic regression to identify factors associated with symptoms of depression or anxiety in care partners, as assessed by Patient Health Questionnaire (PHQ-9) and General Anxiety Disorder (GAD-7) scores, respectively. Results: Depression and anxiety data were available on all 640 care partners. In total, 251 (39.2%) had depression as measured by a score of ≥5 on the PHQ-9 and 299 (46.7%) had anxiety based on a score ≥5 on the GAD-7. Patient functional impairment (OR 1.04, 95% CI 1.01, 1.07), behavioral and psychological symptoms (OR 1.08, 95% CI 1.04, 1.13) and care partner social support (OR 0.91, CI 0.88, 0.95) were significantly associated with care partner depression. Similarly, patient functional impairment (OR 1.04, 95% CI 1.01, 1.07), behavioral and psychological symptoms (OR 1.11, 95% CI 1.07, 1.16) and care partner social support (OR 0.94, CI 0.90, 0.97) were also significantly associated with care partner anxiety as was patient race (p=0.041). Conclusion: Care partners of older adults with CI who present to the ED demonstrate depression and anxiety, but discharge from the ED represents an opportunity to focus on integration of care partners into aftercare in a well-informed, supportive fashion.

Rationale & Objective: Conservative kidney management (CKM) is a viable treatment option for many patients with chronic kidney disease. However, CKM practices and resources in the United States are not well described. We undertook this study to gain a better understanding of factors influencing uptake of CKM by describing: (1) characteristics of patients who choose CKM, (2) provider practice patterns relevant to CKM, and (3) CKM resources available to providers. Study Design: Cross-sectional study. Setting & Participants: This study is a cross-sectional analysis of data from US nephrology clinics enrolled in the chronic kidney disease Outcomes and Practice Patterns Study (CKDopps) collected between 2014 and 2020. Data for this study includes chart-abstracted characteristics of patients with an estimated glomerular filtration rate ≤30mL/min/1.73m2 (n=1018) and available information on whether a decision had been made to pursue CKM at the time of kidney failure, patient (n=407) reports of discussions about forgoing dialysis, and provider (n=26) responses about CKM delivery and available resources in their health systems. Analytical Approach: Descriptive statistics were used to report patient demographics, clinical information, provider demographics, and clinic characteristics. Results: Among data from 1018 patients, 68 (7%) were recorded as planning for CKM. These patients were older, had more comorbidities, and were more likely to require assistance with transfers. Of the 407 patient surveys, 18% reported a conversation about forgoing dialysis with their nephrologist. A majority of providers felt comfortable discussing CKM; however, no clinics had a dedicated clinic or protocol for CKM. Limitations: Inconsistent survey terminology and unlinked patient and provider responses. Conclusions: Few patients reported discussion of forgoing dialysis with their providers and even fewer anticipated a choice of CKM on reaching kidney failure. Most providers were comfortable discussing CKM, but practiced in clinics that lacked dedicated resources. Further research is needed to improve the implementation of a CKM pathway. Plain-Language Summary: For older comorbid adults with kidney failure, conservative kidney management (CKM) can be an appropriate treatment choice. CKM is a holistic approach with treatment goals of maximizing quality of life and preventing progression of chronic kidney disease (CKD) without initiation of dialysis. We investigated US CKM practices and found that among 1018 people with CKD, only 7% were planning for CKM. Of 407 surveyed patients, 18% reported a conversation with their provider about forgoing dialysis. In contrast, most providers felt comfortable discussing CKM; however, none reported working in an environment with a dedicated CKM clinic or protocol. Our data show the need for further CKM education in the United States as well as dedicated resources for its delivery.

Abstract The coronavirus disease 2019 (COVID-19) has developed into a pandemic. Data-driven techniques can be used to inform and guide public health decision- and policy-makers. In generalizing the spread of a virus over a large area, such as a province, it must be assumed that the transmission occurs as a stochastic process. It is therefore very difficult for policy and decision makers to understand and visualize the location specific dynamics of the virus on a more granular level. A primary concern is exposing local virus hot-spots, in order to inform and implement non-pharmaceutical interventions. A hot-spot is defined as an area experiencing exponential growth relative to the generalised growth of the pandemic. This paper uses the first and second waves of the COVID-19 epidemic in Gauteng Province, South Africa, as a case study. The study aims provide a data-driven methodology and comprehensive case study to expose location specific virus dynamics within a given area. The methodology uses an unsupervised Gaussian Mixture model to cluster cases at a desired granularity. This is combined with an epidemiological analysis to quantify each cluster’s severity, progression and whether it can be defined as a hot-spot.

BackgroundPrediabetes affects 26.4 million people aged 65 years or older (48.8%) in the United States. Although older adults respond well to the evidence-based Diabetes Prevention Program, they are a heterogeneous group with differing physiological, biomedical, and psychosocial needs who can benefit from additional support to accommodate age-related changes in sensory and motor function. ObjectiveThe purpose of this paper is to describe adaptations of the Centers for Disease Control and Prevention’s Diabetes Prevention Program aimed at preventing diabetes among older adults (ages ≥65 years) and findings from a pilot of 2 virtual sessions of the adapted program that evaluated the acceptability of the content. MethodsThe research team adapted the program by incorporating additional resources necessary for older adults. A certified lifestyle coach delivered 2 sessions of the adapted content via videoconference to 189 older adults. ResultsThe first session had a 34.9% (38/109) response rate to the survey, and the second had a 34% (30/88) response rate. Over three-quarters (50/59, 85%) of respondents agreed that they liked the virtual program, with 82% (45/55) agreeing that they would recommend it to a family member or a friend. ConclusionsThis data will be used to inform intervention delivery in a randomized controlled trial comparing in-person versus virtual delivery of the adapted program.

In the Diabetes Prevention Program (DPP) randomized, controlled clinical trial, participants who were ≥ 60 years of age in the intensive lifestyle (diet and physical activity) intervention had a 71% reduction in incident diabetes over the 3-year trial. However, few of the 26.4 million American adults age ≥65 years with prediabetes are participating in the National DPP. The BRInging the Diabetes prevention program to GEriatric Populations (BRIDGE) randomized trial compares an in-person DPP program Tailored for Older AdulTs (DPP-TOAT) to a DPP-TOAT delivered via group virtual sessions (V-DPP-TOAT) in a randomized, controlled trial design (N = 230). Eligible patients are recruited through electronic health records (EHRs) and randomized to the DPP-TOAT or V-DPP-TOAT arm. The primary effectiveness outcome is 6-month weight loss and the primary implementation outcome is intervention session attendance with a non-inferiority design. Findings will inform best practices in the delivery of an evidence-based intervention.

Abstract Background The need to engage adults, age 65 and older, in clinical trials of conditions typical in older populations, (e.g. hypertension, diabetes mellitus, Alzheimer’s disease and related dementia) is exponentially increasing. Older adults have been markedly underrepresented in clinical trials, often exacerbated by exclusionary study criteria as well as functional dependencies that preclude participation. Such dependencies may further exacerbate communication challenges. Consequently, the evidence of what works in subject recruitment is less generalizable to older populations, even more so for those from racial and ethnic minority and low-income communities. Methods To support capacity of research staff, we developed a virtual, three station simulation (Group Objective Structured Clinical Experience—GOSCE) to teach research staff communication skills. This 2-h course included a discussion of challenges in recruiting older adults; skills practice with Standardized Participants (SPs) and faculty observer who provided immediate feedback; and debrief to highlight best practices. Each learner had opportunities for active learning and observational learning. Learners completed a retrospective pre-post survey about the experience. SP completed an 11-item communication checklist evaluating the learner on a series of established behaviorally anchored communication skills (29). Results In the research staff survey, 92% reported the overall activity taught them something new; 98% reported it provided valuable feedback; 100% said they would like to participate again. In the SP evaluation there was significant variation: the percent well-done of items by case ranged from 25–85%. Conclusions Results from this pilot suggest that GOSCEs are a (1) acceptable; (2) low cost; and (3) differentiating mechanism for training and assessing research staff in communication skills and structural competency necessary for participant research recruitment.

Abstract The advancement of microgravity simulators is helping many researchers better understanding the impact of the mechanically unloaded space environment on cellular function and disfunction. However, performing microgravity experiments on Earth, using simulators such as the Random Positioning Machine, introduces some unique practical challenges, including air bubble formation and leakage of growth medium from tissue culture flask and plates, all of which limit research progress. Here, we developed an easy-to-use hybrid biological platform designed with the precision of 3D printing technologies combined with PDMS microfluidic fabrication processes to facilitate reliable and reproducible microgravity cellular experiments. The system has been characterized for applications in the contest of brain cancer research by exposing glioblastoma and endothelial cells to 24 h of simulated microgravity condition to investigate the triggered mechanosensing pathways involved in cellular adaptation to the new environment. The platform demonstrated compatibility with different biological assays, i.e., proliferation, viability, morphology, protein expression and imaging of molecular structures, showing advantages over the conventional usage of culture flask. Our results indicated that both cell types are susceptible when the gravitational vector is disrupted, confirming the impact that microgravity has on both cancer and healthy cells functionality. In particular, we observed deactivation of Yap-1 molecule in glioblastoma cells and the remodeling of VE-Cadherin junctional protein in endothelial cells. The study provides support for the application of the proposed biological platform for advancing space mechanobiology research, also highlighting perspectives and strategies for developing next generation of brain cancer molecular therapies, including targeted drug delivery strategies.

Facial Feminization Surgery (FFS) is a transformative surgical approach aimed at aligning the facial features of transgender women with their gender identity. Through a systematic analysis, this paper explores the clinical differences between male and female facial skeletons along with the craniofacial techniques employed in FFS for each region. The preoperative planning stage is highlighted, emphasizing the importance of virtual planning and AI morphing as valuable tools to be used to achieve surgical precision. Consideration is given to special circumstances, such as procedure sequencing for older patients and silicone removal. Clinical outcomes, through patient-reported outcome measures and AI-based gender-typing assessments, showcase the efficacy of FFS in achieving proper gender recognition and alleviating gender dysphoria. This comprehensive review not only offers valuable insights into the current state of knowledge regarding FFS but also emphasizes the potential of artificial intelligence in outcome evaluation and surgical planning to further advance patient care and satisfaction with FFS.

BackgroundAlcohol and drug use (substance use) is a risk factor for crash involvement.ObjectivesTo assess the association between substance use and crash injury severity among older adults and how the relationship differs by rurality/urbanicity.MethodsWe pooled 2017-2021 cross-sectional data from the United States National Emergency Medical Service (EMS) Information System. We measured injury severity (low acuity, emergent, critical, and fatal) predicted by substance use, defined as self-reported or officer-reported alcohol and/or drug use. We controlled for age, sex, race/ethnicity, road user type, anatomical injured region, roadway crash, rurality/urbanicity, time of the day, and EMS response time. We performed a partial proportional ordinal logistic regression and reported the odds of worse injury outcomes (emergent, critical, and fatal injuries) compared to low acuity injuries, and the predicted probabilities by rurality/urbanicity.ResultsOur sample consisted of 252,790 older adults (65 years and older) road users. Approximately 67%, 25%, 6%, and 1% sustained low acuity, emergent, critical, and fatal injuries, respectively. Substance use was reported in approximately 3% of the population, and this proportion did not significantly differ by rurality/urbanicity. After controlling for patient, crash, and injury characteristics, substance use was associated with 36% increased odds of worse injury severity. Compared to urban areas, the predicted probabilities of emergent, critical, and fatal injuries were higher in rural and suburban areas.ConclusionSubstance use is associated with worse older adult crash injury severity and the injury severity is higher in rural and suburban areas compared to urban areas.

BackgroundOlder adults with cognitive impairment have more emergency department visits and 30-day readmissions and are more likely to die after visiting the emergency department than people without cognitive impairment. Emergency department providers frequently do not identify cognitive impairment. Use of cognitive screening tools, along with better understanding of root causes for emergency department visits, could equip health care teams with the knowledge needed to develop individually tailored care management strategies for post–emergency department care. By identifying and directly addressing patients’ and informal caregivers’ (or care partners’) psychosocial and health care needs, such strategies could reduce the need for repeat acute care. We have used the terms “caregiver” and “care partner” interchangeably. ObjectiveWe aimed to describe the protocol for a randomized controlled trial of a new care management intervention, the Program of Intensive Support in Emergency Departments for Care Partners of Cognitively Impaired Patients (POISED) trial, compared with usual care. We described the research design, intervention, outcome measures, data collection techniques, and analysis plans. MethodsEmergency department patients who were aged ≥75 years and screened positive for cognitive impairment via either the Mini-Cog or the proxy-reported Short Informant Questionnaire on Cognitive Decline in the Elderly, with a planned discharge to home, were recruited to participate with their identified informal (family or friend) caregiver in the 2-site POISED randomized controlled trial at New York University Langone Health and Indiana University. The intervention group received 6 months of care management from the POISED Care Team of registered nurses and specialty-trained paraprofessionals, who perform root cause analyses, administer standardized assessments, provide advice, recommend appropriate referrals, and, when applicable, implement dementia-specific comorbid condition protocols. The control group received care as recommended at emergency department discharge (usual care) and were given information about resources for further cognitive assessment. The primary outcome is repeat emergency department use; secondary outcomes include caregiver activation for patient health care management, caregiver depression, anxiety, and experience of social support as important predisposing and time-varying enabling and need characteristics. Data were collected from questionnaires and patients’ electronic health records. ResultsRecruitment was conducted between March 2018 and May 2021. Study findings will be published in peer-reviewed journals and presented to peer audiences, decision makers, stakeholders, and other interested persons. ConclusionsThe POISED intervention is a promising approach to tailoring care management based on root causes for emergency department admission of patients with cognitive impairment with the aim of reducing readmissions. This trial will provide insights for caregivers and emergency department and primary care providers on appropriate, personalized, and proactive treatment plans for older adults with cognitive impairment. The findings will be relevant to audiences concerned with quality of life for individuals with cognitive impairment and their caregivers. Trial RegistrationClinicalTrials.gov NCT03325608; https://clinicaltrials.gov/ct2/show/NCT03325608 International Registered Report Identifier (IRRID)DERR1-10.2196/36607

Background: Oral mucosal conditions are commonly experienced in the general population and can have a negative impact on one’s quality of life. This study evaluated the ability of Australian pharmacists and final-year pharmacy students to recognise and manage these common oral mucosal diseases through the use of case vignettes. Methods: Australian pharmacists and final-year pharmacy students were invited through social media, university learning management systems, or email to complete an online questionnaire consisting of six case vignettes covering topics relating to common oral mucosal presentations. Results: A total of 65 pharmacists and 78 students completed the questionnaire. More than 50% of the participants reported having seen all types of oral mucosal presentations, except for denture stomatitis, in their practice. The provision of best practice recommendations was reported by only 14%, 15%, 8%, and 6% of the participants for geographic tongue, hairy tongue, angular cheilitis, and denture-associated stomatitis, respectively, whereas 82% offered an appropriate anti-viral treatment for cold sore and 33% provided the best practice recommendations for oral thrush. Conclusion: This study emphasised the importance of further developing and integrating best practice oral healthcare training programs specifically tailored to the Australian pharmacy profession.

Do lymphatic vessels support cancer cells? Or are they vessels that help suppress cancer development? It is known that the lymphatic system is a vehicle for tumor metastasis and that the lymphangiogenic regulator VEGF-C supports the tumor. One such role of VEGF-C is the suppression of the immune response to cancer. The lymphatic system has also been correlated with an increase in interstitial fluid pressure of the tumor microenvironment. On the other hand, lymphatic vessels facilitate immune surveillance to mount an immune response against tumors with the support of VEGF-C. Furthermore, the activation of lymphatic fluid drainage may prove to filter and decrease tumor interstitial fluid pressure. In this review, we provide an overview of the dynamic between lymphatics, cancer, and tumor fluid pressure to suggest that lymphatic vessels may be used as an antitumor therapy due to their capabilities of immune surveillance and fluid pressure drainage. The application of this potential may help to prevent tumor proliferation or increase the efficacy of drugs that target cancer.

BackgroundHomebound individuals with advanced Parkinson disease (PD) require intensive caregiving, the majority of which is provided by informal, family caregivers. PD caregiver strain is an independent risk factor for institutionalization. There are currently no effective interventions to support advanced PD caregivers. Studies in other neurologic disorders, however, have demonstrated the potential for peer mentoring interventions to improve caregiver outcomes. In the context of an ongoing trial of interdisciplinary home visits, we designed and piloted a nested trial of caregiver peer mentoring for informal caregivers of individuals with advanced PD. ObjectiveThe aim of this study was to test the feasibility of peer mentoring for caregivers of homebound individuals with advanced PD and to evaluate its effects on anxiety, depression, and caregiver strain. MethodsThis was a single-center, 16-week pilot study of caregiver peer mentoring nested within a year-long controlled trial of interdisciplinary home visits. We recruited 34 experienced former or current family caregivers who completed structured mentor training. Caregivers enrolled in the larger interdisciplinary home visit trial consented to receive 16 weeks of weekly, one-to-one peer mentoring calls with a trained peer mentor. Weekly calls were guided by a curriculum on advanced PD management and caregiver support. Fidelity to and satisfaction with the intervention were gathered via biweekly study diaries. Anxiety, depression, and caregiver strain were measured pre- and postmentoring intervention at home visits 2 and 3. ResultsEnrollment and peer-mentor training began in 2018, and 65 caregivers enrolled in the overarching trial. The majority of mentors and mentees were White, female spouses or partners of individuals with PD; mentors had a mean of 8.7 (SD 6.4) years of caregiving experience, and 33 mentors were matched with at least 1 mentee. ConclusionsThis is the first study of caregiver peer mentoring in PD and may establish an adaptable and sustainable model for disease-specific caregiver interventions in PD and other neurodegenerative diseases. Trial RegistrationClinicalTrials.gov NCT03189459; http://clinicaltrials.gov/ct2/show/NCT03189459 International Registered Report Identifier (IRRID)DERR1-10.2196/34750

Pluchea indica (L.) Less. is a perennial plant known for its versatile uses in traditional medicine. Previous findings have shown that the extracts of Pluchea indica possess significant anti-inflammatory, anti-ulcer and anti-tuberculosis activity. The aim of this study was to demonstrate the anticancer activity of the hexane fraction of P. indica root extract (H-PIRE) in human glioblastoma cells using flow cytometric and western blot analysis. The results shoewd that, H-PIRE suppressed the growth of glioblastoma cells in a dose-dependent manner. H-PIRE treatment markedly decreased the population of cells in S and G2/M phases. The significant upregulation of acidic vesicular organelle (AVO) was detected during H-PIRE treatment. The expression levels of microtubule-associated light chain 3-II (LC3-II) protein, phosphorylated JNK and phosphorylated p38 were significantly increased, confirming the occurrence of autophagy during the process. Finally, the combination treatment of H-PIRE and LY294002, a pan PI3K inhibitor, further decreased cell viability, suggesting an additive anticancer effect. Taken together, our results suggest that H-PIRE suppresses the proliferation of glioblastoma cells by inducing cell cycle arrest and autophagy. [ABSTRACT FROM AUTHOR]

With the advancement in reusable rocket propulsion technology, space tourist trips into outer space are now becoming a possibility at a cost-effective rate. As such, astronauts will face a host of health-related challenges, particularly on long-duration space missions where maintaining a balanced healthy microbiome is going to be vital for human survival in space exploration as well as mission success. The human microbiome involves a whole list of micro-organisms that reside in and on the human host, and plays an integral role in keeping the human host healthy. However, imbalances in the microbiome have been directly linked to many human diseases. Research findings have clearly shown that the outer space environment can directly affect the normal microbiome of astronauts when the astronaut is exposed to the microgravity environment. In this study, we show that the simulation of microgravity on earth can mimic the outer space microgravity environment. Staphylococus aureus (S. aureus) was chosen for this study as it is an opportunistic pathogen, which is part of the normal human skin microflora and the nasal passages. This study’s results show that S. aureus proliferation was significantly increased under a microgravity environment compared to Earth’s gravity conditions, which complements previous work performed on bacteria in the outer space environment in the International Space Station (ISS). This demonstrates that this technology can be utilised here on Earth to mimic the outer space environment and to study challenging health-related questions. This in return saves us the cost on conducting experiments in the ISS and can help advance knowledge at a faster rate and produce countermeasures to mitigate the negative side effects of the hostile outer space environment on humans.

In recent years, there has been an increasing interest in space exploration, supported by the accelerated technological advancements in the field. This has led to a new potential environment that humans could be exposed to in the very near future, and therefore an increasing request to evaluate the impact this may have on our body, including health risks associated with this endeavor. A critical component in regulating the human pathophysiology is represented by the cardiovascular system, which may be heavily affected in these extreme environments of microgravity and radiation. This mini review aims to identify the impact of microgravity and radiation on the cardiovascular system. Being able to understand the effect that comes with deep space explorations, including that of microgravity and space radiation, may also allow us to get a deeper understanding of the heart and ultimately our own basic physiological processes. This information may unlock new factors to consider with space exploration whilst simultaneously increasing our knowledge of the cardiovascular system and potentially associated diseases.

A recent development in the production of lightweight concrete is the use of bubble or hollow aggregates. Due to its exceptional energy absorption and ductility properties, engineered cementitious composite (ECC) is increasingly recommended and used for structural applications, particularly in earthquake-prone regions. As a result, researchers have started looking into the benefits of lightweight ECC for such applications. However, the strength is considerably compromised due to the use of lightweight fillers such as perlite, cenospheres, glass microbubbles, and crumb rubber (CR). This study evaluates an origami-shaped bubble aggregate (OBA) novel application in rubberized ECC (RECC) to achieve density reduction at a relatively lower strength loss. The experiment is designed using response surface methodology (RSM) with the spacing of the OBA at 10, 15, and 20 mm and its quantity at 9, 15, and 21 as the input factors (independent variables). The dependent variables (responses) assessed are density, compressive strength, modulus of elasticity, and Poisson’s ratio. The results showed that adding the OBA lowered the density of the RECC by 20%. It was revealed that using up to 15 OBAs with spacings between 15 and 20 mm, a lightweight OBA-RECC with substantial strength could be produced. Similarly, utilizing 15 and 21 OBAs at 20 mm spacing, a lightweight OBA-RECC with a comparable modulus of elasticity as the control could be developed. Models for predicting the responses were developed and validated using analysis of variance (ANOVA) with high R2 values. The spacing and quantity of the OBA’s optimal input levels were determined using the RSM multi-objective optimization to be 20 and 9, respectively. These levels produced optimal responses of 1899 kg/m3, 45.3 MPa, 16.1 GPa, and 0.22 for the density, compressive strength, modulus of elasticity, and Poisson ratio, respectively.

BackgroundThe current understanding of advanced Parkinson disease (PD) and its treatment is largely based on data from outpatient visits. The most advanced and disabled individuals with PD are disconnected from both care and research. A previous pilot study among older, multimorbid patients with advanced PD demonstrated the feasibility of interdisciplinary home visits to reach the target population, improve care quality, and potentially avoid institutionalization. ObjectiveThe aim of this study protocol is to investigate whether interdisciplinary home visits can prevent a decline in quality of life of patients with PD and prevent worsening of caregiver strain. The protocol also explores whether program costs are offset by savings in health care utilization and institutionalization compared with usual care. MethodsIn this single-center, controlled trial, 65 patient-caregiver dyads affected by advanced PD (Hoehn and Yahr stages 3-5 and homebound) are recruited to receive quarterly interdisciplinary home visits over 1 year. The 1-year intervention is delivered by a nurse and a research coordinator, who travel to the home, and it is supported by a movement disorder specialist and social worker (both present by video). Each dyad is compared with age-, sex-, and Hoehn and Yahr stage–matched control dyads drawn from US participants in the longitudinal Parkinson’s Outcome Project registry. The primary outcome measure is the change in patient quality of life between baseline and 1 year. Secondary outcome measures include changes in Hoehn and Yahr stage, caregiver strain, self-reported fall frequency, emergency room visits, hospital admissions, and time to institutionalization or death. Intervention costs and changes in health care utilization will be analyzed in a budget impact analysis to explore the potential for model adaptation and dissemination. ResultsThe protocol was funded in September 2017 and approved by the Rush Institutional Review Board in October 2017. Recruitment began in May 2018 and closed in November 2019 with 65 patient-caregiver dyads enrolled. All study visits have been completed, and analysis is underway. ConclusionsTo our knowledge, this is the first controlled trial to investigate the effects of interdisciplinary home visits among homebound individuals with advanced PD and their caregivers. This study also establishes a unique cohort of patients from whom we can study the natural course of advanced PD, its treatments, and unmet needs. Trial RegistrationClinicalTrials.gov NCT03189459; http://clinicaltrials.gov/ct2/show/NCT03189459. International Registered Report Identifier (IRRID)PRR1-10.2196/31690

Abstract Background The purpose of this 6-week intervention was to test the feasibility and acceptability of implementing a telehealth-adapted Diabetes Prevention Program (DPP) at a senior center. Methods Older adults (n = 16) attended weekly interactive webinars. At each measurement time point, participants completed questionnaires covering lifestyle, physical activity, quality of life, and food records and wore physical activity trackers. Qualitative data were gathered from 2 focus groups inviting all 16 participants with 13 and 10 participants attending, respectively. Results Over 2000 senior center members were contacted, approximately 2% (n = 39) responded to the recruitment email, and 16 were recruited into the study. Retention was 75%, and attendance rates averaged 80% across the six intervention sessions. The focus group participants provided positive opinions for most program components, especially the webinar group interaction and using physical activity trackers. Suggestions for improvement included a greater focus on specific needs of older adults (i.e., adapting activities) and placing a greater emphasis on dietary strategies to prevent diabetes. Mean weight loss was 2.9% (2.7 kg [95% CI 1.6, 3.7]; p value = 0.001). Conclusion The feasibility of providing DPP via webinar appears to be high based on the retention and attendance rates. Similar to other behavioral interventions engaging older adults, recruitment rates were low. Acceptability was evidenced by high attendance at the intervention sessions and feedback from participants during focus group sessions. The intervention efficacy should be evaluated based on CDC criteria for program recognition in a larger scale randomized trial. Trial registration NCT03524404. Registered 14 May 2018—retrospectively registered. Trial protocol will be provided by the corresponding author upon request.

This study investigates the digital divide in Canada related to access to online government services. Since digital equity can have welfare implications, it is an important area to explore. We use a bivariate logit model to estimate the determinants of access to e-government services. The results show significant disadvantages for females, those who cannot speak official languages, those living in rural areas and those in the lower quantiles of household income. Public policy measures such as infrastructure development in rural areas, improvement in digital equity and streamlining of e-government access can help address this issue.

Summary: The deleterious effects of psychological stress on mainstream T lymphocytes are well documented. However, how stress impacts innate-like T cells is unclear. We report that long-term stress surprisingly abrogates both T helper 1 (TH1)- and TH2-type responses orchestrated by invariant natural killer T (iNKT) cells. This is not due to iNKT cell death because these cells are unusually refractory to stress-inflicted apoptosis. Activated iNKT cells in stressed mice exhibit a “split” inflammatory signature and trigger sudden serum interleukin-10 (IL-10), IL-23, and IL-27 spikes. iNKT cell dysregulation is mediated by cell-autonomous glucocorticoid receptor signaling and corrected upon habituation to predictable stressors. Importantly, under stress, iNKT cells fail to potentiate cytotoxicity against lymphoma or to reduce the burden of metastatic melanoma. Finally, stress physically spares mouse mucosa-associated invariant T (MAIT) cells but hinders their TH1-/TH2-type responses. The above findings are corroborated in human peripheral blood and hepatic iNKT/MAIT cell cultures. Our work uncovers a mechanism of stress-induced immunosuppression.

Sex difference is a risk factor for abdominal aortic aneurysm (AAA) formation yet the reason for male predominance remains unclear. Androgen and the androgen receptor (AR) influence the male sex difference, indicating that AR signaling may affect AAA development. Using angiotensin II–induced AAA in apolipoprotein E null mouse models (82.4% AAA incidence), we found that mice lacking AR failed to develop AAA and aorta had dramatically reduced macrophages infiltration and intact elastic fibers. These findings suggested that AR expression in endothelial cells, macrophages, or smooth muscle cells might play a role in AAA development. Selective knockout of AR in each of these cell types further demonstrated that mice lacking AR in macrophages (20% AAA incidence) or smooth muscle cells (12.5% AAA incidence) but not in endothelial cells (71.4% AAA incidence) had suppressed AAA development. Mechanism dissection showed that AR functioned through modulation of interleukin-1α (IL-1α) and transforming growth factor-β1 signals and by targeting AR with the AR degradation enhancer ASC-J9 led to significant suppression of AAA development. These results demonstrate the underlying mechanism by which AR influences AAA development is through IL-1α and transforming growth factor-β1, and provides a potential new therapy to suppress/prevent AAA by targeting AR with ASC-J9. [ABSTRACT FROM AUTHOR]

Multiple studies show that racial and ethnic minorities with low socioeconomic status are diagnosed with Alzheimer’s disease and Alzheimer’s disease–related dementias (AD/ADRD) in more advanced disease stages, receive fewer formal services, and have worse health outcomes. For primary care providers confronting this challenge, community-based organizations can be key partners in supporting earlier identification of AD/ADRD and earlier entry into treatment, especially for minority groups. The New York University Center for the Study of Asian American Health, set out to culturally adapt and translate The Kickstart-Assess-Evaluate-Refer (KAER) framework created by the Gerontological Society of America to support earlier detection of dementia in Asian American communities and assist in this community-clinical coordinated care. We found that CBOs play a vital role in dementia care, and are often the first point of contact for concerns around cognitive impairment in ethnically diverse communities. A major strength of these centers is that they provide culturally appropriate group education that focuses on whole group quality of life, rather than singling out any individual. They also offer holistic family-centered care and staff have a deep understanding of cultural and social issues that affect care, including family dynamics. For primary care providers confronting the challenge of delivering evidence-based dementia care in the context of the busy primary care settings, community-based organizations can be key partners in supporting earlier identification of AD/ADRD and earlier entry into treatment, especially for minority groups.

A lack of gravity experienced during space flight has been shown to have profound effects on human physiology including muscle atrophy, reductions in bone density and immune function, and endocrine disorders. At present, these physiological changes present major obstacles to long-term space missions. What is not clear is which pathophysiological disruptions reflect changes at the cellular level versus changes that occur due to the impact of weightlessness on the entire body. This review focuses on current research investigating the impact of microgravity at the cellular level including cellular morphology, proliferation, and adhesion. As direct research in space is currently cost prohibitive, we describe here the use of microgravity simulators for studies at the cellular level. Such instruments provide valuable tools for cost-effective research to better discern the impact of weightlessness on cellular function. Despite recent advances in understanding the relationship between extracellular forces and cell behavior, very little is understood about cellular biology and mechanotransduction under microgravity conditions. This review will examine recent insights into the impact of simulated microgravity on cell biology and how this technology may provide new insight into advancing our understanding of mechanically driven biology and disease.

BackgroundMultiple exercise modalities and mindfulness activities are beneficial in Parkinson's Disease (PD). Karate is a martial art that combines aerobic and large-amplitude movements, balance and core training, and mindfulness, suggesting a potential benefit for individuals with PD from multiple perspectives.ObjectiveTo evaluate the feasibility of community-based Shotokan karate classes involving physical activity and mindfulness among individuals with mild- to moderate-stage PD, and to explore the effects of karate on objective and patient-reported outcomes.MethodsWe conducted a 10-week, unblinded trial of twice weekly, PD-specific karate classes. Feasibility was assessed by: dropout rates, adherence via attendance records, adverse effects and falls, and continued participation six months post-intervention. Participants completed pre- and post-intervention assessments of disease-related quality of life (Parkinson's Disease Questionnaire-8, PDQ-8), falls, and post-intervention assessment of change in overall wellbeing (Patient Global Impression of Change, PGIC), with exploratory measures of mobility using the Timed Up and Go (TUG), mood using the Hospital Anxiety and Depression Scale (HADS), and cognition using digit span forward and backward and the Symbol Digit Modalities Test (SDMT).ResultsOf 19 enrolled participants, 15 completed the study (79%). Among completers, mean adherence was 87% during the ten weeks of intervention, and 53% maintained karate participation six months later and endorsed sustained improvement, respectively. No adverse effects or change in fall frequency were detected. Among completers, 53% were women, and mean PD duration was 6 years (range 2-20). Quality of life improved to a clinically significant degree (PDQ-8: mean 25.3 (standard deviation (SD) 20.8) versus 19.3 (SD 19.6), p = 0.01, effect size 0.83). On the PGIC, 87% endorsed feeling moderately or considerably better. Mobility did not change significantly (TUG: 9.6 seconds (SD 2.23) versus 9.0 seconds (SD 1.89), p = 0.12, effect size 0.43), nor were there changes in overall physical activity, mood, or cognition (p = 0.35-0.92).ConclusionsIn a small, 10-week, unblinded trial of community-based karate classes for individuals with mild and moderate PD, high adherence was noted. Quality of life and wellbeing improved significantly, without changes in exploratory outcomes of mobility or neuropsychological outcomes. The study was underpowered, particularly for the exploratory outcomes. Controlled and longitudinal investigation is warranted to confirm our pilot findings and explore the long-term effects and sustainability of karate in PD.Trial registrationClinicaltrials.gov: NCT03555695.