Human induced mesenchymal stem cells display increased sensitivity to matrix stiffness.

The clinical translation of mesenchymal stem cells (MSCs) is limited by population heterogeneity and inconsistent responses to engineered signals. Specifically, the extent in which MSCs respond to mechanical cues varies significantly across MSC lines. Although induced pluripotent stem cells (iPSCs) have recently emerged as a novel cell source for creating highly homogeneous MSC (iMSC) lines, cellular mechanosensing of iMSCs on engineered materials with defined mechanics is not well understood. Here, we tested the mechanosensing properties of three human iMSC lines derived from iPSCs generated using a fully automated platform. Stiffness-driven changes in morphology were comparable between MSCs and iMSCs cultured atop hydrogels of different stiffness. However, contrary to tissue derived MSCs, no significant changes in iMSC morphology were observed between iMSC lines atop different stiffness hydrogels, demonstrating a consistent response to mechanical signals. Further, stiffness-driven changes in mechanosensitive biomarkers were more pronounced in iMSCs than MSCs, which shows that iMSCs are more adaptive and responsive to mechanical cues than MSCs. This study reports that iMSCs are a promising stem cell source for basic and applied research due to their homogeneity and high sensitivity to engineered mechanical signals

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

EMPTY AND FILLED BOTTLE INSPECTION SYSTEM

Automated Visual Inspection System (AVIS) have a strong ability for quality control in manufacturing industries by inspecting products automatically instead of manual inspections. This paper gives methods for bottle inspection in manufacturing industries. The paper describes mechanism for the defect detection, top and bottom detection, cap placement and fill level inspection. For empty bottle inspection the image is processed by contrast enhancement and then circular Hough transform is used. The location and radius of top and bottom of bottle is analyzed. After filling the bottle with liquid and placing the cap, edge detection method is used which is followed by horizontal line detection to identify whether fill level and cap closure is appropriate or not. Presented bottle inspection system works with 100% accuracy in proper illumination condition

Comorbidities and Risk Factors Associated With Insomnia in the Elderly Population

Introduction/Objectives: Sleep disorders affect around 50 to 70 million Americans, with chronic insomnia being the most common, especially in the elderly population. With an 11-fold increase in the US office visits due to insomnia, from 0.8 to 9.4 million, between 1993 and 2015, it is imperative to identify the modifiable risk factors. The aim of our study was to examine the association of risk factors and comorbid medical conditions with insomnia in patients 65 years, and older. Methods: We performed a retrospective electronic medical record review of the patients aged 65 years and older, who visited our suburban internal medicine office between July 1, 2020 and June 30, 2021. Patients were divided into insomnia group, and the group without insomnia. The associated variables were compared. Results: Among 2431 patients, 247 patients (10.2%) had insomnia. Mean ages of the patients in the insomnia group and the group without insomnia were comparable (77 ± 8.1 year vs 76 ± 7.5 year; P  = .211). There was a significantly greater frequency of women in the insomnia group compared to the group without insomnia (63.2% vs 55.5%; P  = .022). In the insomnia group, there were significantly higher frequencies of association of certain comorbidities compared to the group without insomnia, such as dementia (6.5% vs 3.4%; P  = .015), depression (30.8% vs 14.9%; P  < 0.001), anxiety disorder (34.4% vs 17.4%; P  < .001), atrial fibrillation (19.4% vs 13.4%; P  = .01), and chronic pain disorders (32.8% vs 18.9%; P  < .001). Logistic regression analysis showed significantly greater odds of insomnia in patients who had depression (OR = 1.860, 95% CI 1.342–2.576; P  < .001), anxiety (OR = 1.845, 95% CI 1.342-2.537; P  < .001), and chronic pain disorders (OR = 1.901, 95% CI 1.417-2.549; P  < .001). Conclusions: Female sex, dementia, depression, anxiety, chronic pain disorders, and atrial fibrillation are associated with insomnia in the elderly patients. Presence of depression, anxiety, and chronic pain disorders are associated with greater odds of having insomnia in the elderly patients

Association of Risk Factors and Comorbidities With Chronic Pain in the Elderly Population

Introduction/Objective: Chronic pain disorders affect about 20% of adults in the United States, and it disproportionately affects individuals living in the neighborhoods of extreme socioeconomic disadvantage. In many instances, chronic pain has been noted to arise from an aggregation of multiple risk factors and events. Therefore, it is of importance to recognize the modifiable risk factors. The aim of this study was to investigate the comorbid medical conditions and risk factors associated with chronic pain disorders in patients aged 65 years and older. Methods: Our team retrospectively reviewed medical records of elderly patients (65 years and older) who were evaluated in our outpatient medicine office between July 1, 2020 and June 30, 2021 for acute problems, management of chronic medical problems, or well visits. We divided our patients into a group who suffered from chronic pain disorder, and another group who did not have chronic pain disorder. The association of variables were compared between those groups. Results: Of the 2431 patients, 493 (20.3%) had a chronic pain disorder. A higher frequency of females in the group with chronic pain disorder was found compared to the group without a chronic pain disorder (60.6% vs 55.2%; P  = .033). The mean ages between the two groups were similar in the group with a chronic pain disorder compared to the group without (76.35 ± 7.5 year vs 76.81 ± 7.59 year; P  = .228). There were significant associations of certain comorbidities in the group with a chronic pain disorder compared to the group without a chronic pain disorder, such as depression (21.9% vs 15.2%; P  < .001), anxiety (27.0% vs 17.1%; P  < .001), chronic obstructive pulmonary disease (8.7% vs 6.1%; P  = .036), obstructive sleep apnea (16.8% vs 11.6%; P  = .002), gastroesophageal reflux disease (40.8% vs 29.0%; P  < .001), osteoarthritis (49.3% vs 26.1%; P  < .001), other rheumatologic diseases (24.9% vs 19.4%; P  = .006), and peripheral neuropathy (14.4% vs 5.3%; P  < .001). Conclusion: Female sex, depression, anxiety, chronic obstructive pulmonary disease, obstructive sleep apnea, gastroesophageal reflux disease, osteoarthritis, other rheumatologic diseases, and peripheral neuropathy were significantly associated with chronic pain disorder in elderly patients, while BMI was not associated with chronic pain disorder

Risk Factors Associated With Atrial Fibrillation in Elderly Patients.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia with a growing prevalence worldwide, especially in the elderly population. Patients with AF are at higher risk of serious life-threatening events and complications that may lead to long-term sequelae and reduce quality of life. The aim of our study was to examine the association of additional risk factors and comorbid medical conditions with AF in patients 65 years, or older. METHODS: We performed a retrospective electronic medical record review of patients aged 65 years and older, who visited our internal medicine office between July 1, 2020 and June 30, 2021. RESULTS: Among 2,433 patients, 418 patients (17.2%) had AF. Our analysis showed that for each unit increased in age, there was a 4.5% increase in the odds of AF (95% confidence interval (CI) 2.2-6.9%; P \u3c 0.001). Compared to patients of Caucasian descent, African-American patients had significantly decreased odds of AF (odds ratio (OR) 0.274, 95% CI 0.141 - 0.531; P \u3c 0.001). Patients with hypertension had 2.241 greater odds of AF (95% CI 1.421 - 3.534; P = 0.001). Additional comorbidities with significantly greater odds of AF included other cardiac arrhythmias (OR 2.523, 95% CI 1.720 - 3.720; P \u3c 0.001), congestive heart failure (OR 3.111, 95% CI 1.674 - 5.784; P \u3c 0.001), osteoarthritis (OR 3.014, 95% CI 2.138 - 4.247; P \u3c 0.001), liver disease (OR 2.129, 95% CI 1.164 - 3.893; P = 0.014), and colorectal disease (OR 1.500 95% CI 1.003 - 2.243; P = 0.048). Comorbidities with significantly decreased odds of AF included other rheumatological disorder (OR 0.144, 95% CI 0.086 - 0.243; P \u3c 0.001), non-steroidal anti-inflammatory drugs (NSAIDs) use (OR 0.206, 95% CI 0.125 - 0.338; P \u3c 0.001), and corticosteroid use (OR 0.553, 95% CI 0.374 - 0.819; P = 0.003). CONCLUSIONS: Increasing age, hypertension, presence of other cardiac arrhythmias, congestive heart failure, osteoarthritis, liver disease, and colorectal disease are associated with increased odds of having AF

Impact of the COVID-19 pandemic on patients with paediatric cancer in low-income, middle-income and high-income countries: a multicentre, international, observational cohort study

OBJECTIVES: Paediatric cancer is a leading cause of death for children. Children in low-income and middle-income countries (LMICs) were four times more likely to die than children in high-income countries (HICs). This study aimed to test the hypothesis that the COVID-19 pandemic had affected the delivery of healthcare services worldwide, and exacerbated the disparity in paediatric cancer outcomes between LMICs and HICs. DESIGN: A multicentre, international, collaborative cohort study. SETTING: 91 hospitals and cancer centres in 39 countries providing cancer treatment to paediatric patients between March and December 2020. PARTICIPANTS: Patients were included if they were under the age of 18 years, and newly diagnosed with or undergoing active cancer treatment for Acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, Wilms' tumour, sarcoma, retinoblastoma, gliomas, medulloblastomas or neuroblastomas, in keeping with the WHO Global Initiative for Childhood Cancer. MAIN OUTCOME MEASURE: All-cause mortality at 30 days and 90 days. RESULTS: 1660 patients were recruited. 219 children had changes to their treatment due to the pandemic. Patients in LMICs were primarily affected (n=182/219, 83.1%). Relative to patients with paediatric cancer in HICs, patients with paediatric cancer in LMICs had 12.1 (95% CI 2.93 to 50.3) and 7.9 (95% CI 3.2 to 19.7) times the odds of death at 30 days and 90 days, respectively, after presentation during the COVID-19 pandemic (p<0.001). After adjusting for confounders, patients with paediatric cancer in LMICs had 15.6 (95% CI 3.7 to 65.8) times the odds of death at 30 days (p<0.001). CONCLUSIONS: The COVID-19 pandemic has affected paediatric oncology service provision. It has disproportionately affected patients in LMICs, highlighting and compounding existing disparities in healthcare systems globally that need addressing urgently. However, many patients with paediatric cancer continued to receive their normal standard of care. This speaks to the adaptability and resilience of healthcare systems and healthcare workers globally

Twelve-month observational study of children with cancer in 41 countries during the COVID-19 pandemic

Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality