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Many germ line diseases stem from a relatively minor disturbance in mutant protein endoplasmic reticulum (ER) 3D assembly. Chaperones are recruited which, on failure to correct folding, sort the mutant for retrotranslocation and cytosolic proteasomal degradation (ER-associated degradation-ERAD), to initiate/exacerbate deficiency-disease symptoms. Several bacterial (and plant) subunit toxins, retrograde transport to the ER after initial cell surface receptor binding/internalization. The A subunit has evolved to mimic a misfolded protein and hijack the ERAD membrane translocon (dislocon), to effect cytosolic access and cytopathology. We show such toxins compete for ERAD to rescue endogenous misfolded proteins. Cholera toxin or verotoxin (Shiga toxin) containing genetically inactivated (± an N-terminal polyleucine tail) A subunit can, within 2-4 hrs, temporarily increase F508delCFTR protein, the major cystic fibrosis (CF) mutant (5-10x), F508delCFTR Golgi maturation (

With the lack of specific signs and symptoms, pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at late metastatic stages, resulting in poor survival outcomes. Among various biomarkers, microRNA-21 (miR-21), a small non-coding RNA, is highly expressed in PDAC. By inhibiting regulatory proteins at the 3′ untranslated regions (UTR), miR-21 holds significant roles in PDAC cell proliferation, epithelial–mesenchymal transition, angiogenesis, as well as cancer invasion, metastasis, and resistance therapy. We conducted a systematic search across major databases for articles on miR-21 and pancreatic cancer mainly published within the last decade, focusing on their diagnostic, prognostic, therapeutic, and biological roles. This rigorous approach ensured a comprehensive review of miR-21’s multifaceted role in pancreatic cancers. In this review, we explore the current understandings and future directions regarding the regulation, diagnostic, prognostic, and therapeutic potential of targeting miR-21 in PDAC. This exhaustive review discusses the involvement of miR-21 in proliferation, epithelial–mesenchymal transition (EMT), apoptosis modulation, angiogenesis, and its role in therapy resistance. Also discussed in the review is the interplay between various molecular pathways that contribute to tumor progression, with specific reference to pancreatic ductal adenocarcinoma.

Background: Adolescents with physical disabilities of childhood often require a transition from pediatric to adult systems as part of life-long, comprehensive health care once they reach 18 years of age. The process of transition can be complex, challenging, and influenced by health-related factors and availability of health care resources. Objective: To provide a baseline profile of health-related quality of life, health management, social participation, and health care utilization for adolescents 16 years of age with spina bifida (SB), acquired brain injury (ABI), or cerebral palsy (CP) in Toronto, Canada. Methods: A cross-sectional survey design was used. A sample was drawn from a large, urban pediatric rehabilitation hospital as part of a prospective, longitudinal, observational mixed-methods study. Seven English language, paper-copy standardized measures were completed; measures were organized across the three domains of interest. Health care utilization data were obtained from population-based, health services administrative datasets held by ICES. These data included outpatient physician visits, emergency department visits, and hospitalizations over a 12-month period, beginning at their 16th birthday. Results: The sample comprised 99 participants: survey measures were completed by 59 participants (12 SB, 19 ABI, and 28 CP) and health care utilization obtained for 92 participants (19 SB, 25 ABI, and 48 CP). Baseline scores across measures and rates of health care utilization are provided. All three groups reported relatively good health-related quality of life. Youth with CP had lower scores on health utility, health management, and social participation, compared with the SB and ABI groups. Youth with SB had slightly higher health care utilization in the 12-month period after their 16th birthday, compared with the ABI and CP groups. Conclusions: This cross-sectional survey collected comprehensive health status and health care utilization data on 16-year-old youth with SB, ABI, and CP in Toronto, Canada. With few exceptions, the CP group consistently scored lower across measurement domains. These baseline data may be useful for hospital administrators, policy makers, and researchers examining changes in health-related quality of life, health management, social participation, and health care utilization among youth with SB, ABI, and CP, particularly in the context of transition planning and evaluation.

Objective: In the fight against COVID-19, vaccination is vital in achieving herd immunity. Many Asian countries are starting to vaccinate frontline workers; however, expedited vaccine development has led to hesitancy among the general population. We evaluated the willingness of healthcare workers to receive the COVID-19 vaccine. Methods: From 12 to 21 December 2020, we recruited 1720 healthcare workers from 6 countries: China, India, Indonesia, Singapore, Vietnam and Bhutan. The self-administrated survey collected information on willingness to vaccinate, perception of COVID-19, vaccine concerns, COVID-19 risk profile, stigma, pro-socialness scale, and trust in health authorities. Results: More than 95% of the healthcare workers surveyed were willing to vaccinate. These respondents were more likely to perceive the pandemic as severe, consider the vaccine safe, have less financial concerns, less stigmatization regarding the vaccine, higher pro-socialness mindset and trust in health authorities. A high perceived pandemic risk index, low vaccine harm index and high pro-socialness index were independent predictors in multivariable analysis. Conclusions: The majority of healthcare workers in Asia are willing to receive COVID-19 vaccination. Perceived COVID-19 susceptibility, low potential risk of vaccine harm and pro-socialness are the main drivers. These findings may help formulate vaccination strategies in other countries.

Home care is an important service for persons with neurological conditions, but little is known about factors affecting health care costs in this setting. Using administrative data collected with the Resident Assessment Instrument for Home Care (RAI-HC), this study identified factors associated with home care costs for recipients of home care services with Alzheimer disease or related dementias, multiple sclerosis, and/or amyotrophic lateral sclerosis. As part of this study, the effectiveness of the Resource Utilization Groups for Home Care (RUG-III/HC), a case-mix classification system developed for the RAI-HC, in predicting care costs for this population, was also tested. Clinical characteristics indicative of greater disease severity had high levels of significance in predicting home care costs. In particular, the RUG-III/HC was highly predictive of home care costs for 3 neurological conditions, indicating the validity of this case-mix system for this population. With the increasing prevalence of neurological conditions and demand for home care services, future studies should continue to focus on identifying specific predictors care costs for those with neurological conditions in this care setting.

Introduction Many Canadians prefer to remain in the community at end-of-life, and to die at home. To do so, early and integrated palliative care (PC) is needed to provide individuals with care and support services across care settings. Measuring access to PC can help to evaluate progress over time. Objectives and Approach This presentation will show findings from our study on whether Canadian decedents had access to PC in the last year of life. Data from physician billings, drug claims, home care, long-term care and acute care were linked to identify decedents and PC service use. These data were also used to examine how PC may affect, or be affected by other interactions with the health system, including inpatient alternate level care days, admissions from long-term care, emergency department visits and stays in intensive care units. Gaps in data availability and quality will also be highlighted. Results About 70% of decedents were identified using administrative health data, although there were variations across jurisdictions due to differences in data availability and quality (9%-81%). For decedents identified across care settings, few received PC in the community in their last year of life, ranging from 4% in long-term care to 12% in home care. More decedents were identified as palliative in acute care (44%) but only one-third received PC in another setting despite multiple interactions with the health system in the last year of life. Those who had integrated, community-based PC were less likely to have a stay in an intensive care unit, and more likely to die in the community. However, few Canadian decedents had access to this type of care. Conclusion/Implications Data linkage identified opportunities for earlier integration of PC and improved care transitions. However, lack of common definitions of PC across sectors and jurisdictions, limitations in data availability and issues in PC coding were identified. Improvements in PC data are required to evaluate progress for the future.