A micropillar array-based microfluidic chip for label-free separation of circulating tumor cells: The best micropillar geometry?

Introduction The information derived from the number and characteristics of circulating tumor cells (CTCs), is crucial to ensure appropriate cancer treatment monitoring. Currently, diverse microfluidic platforms have been developed for isolating CTCs from blood, but it remains a challenge to develop a low-cost, practical, and efficient strategy. Objectives This study aimed to isolate CTCs from the blood of cancer patients via introducing a new and efficient micropillar array-based microfluidic chip (MPA-Chip), as well as providing prognostic information and monitoring the treatment efficacy in cancer patients. Methods We fabricated a microfluidic chip (MPA-Chip) containing arrays of micropillars with different geometries (lozenge, rectangle, circle, and triangle). We conducted numerical simulations to compare velocity and pressure profiles inside the micropillar arrays. Also, we experimentally evaluated the capture efficiency and purity of the geometries using breast and prostate cancer cell lines as well as a blood sample. Moreover, the device’s performance was validated on 12 patients with breast cancer (BC) in different states. Results The lozenge geometry was selected as the most effective and optimized micropillar design for CTCs isolation, providing high capture efficiency (>85 %), purity (>90 %), and viability (97 %). Furthermore, the lozenge MPA-chip was successfully validated by the detection of CTCs from 12 breast cancer (BC) patients, with non-metastatic (median number of 6 CTCs) and metastatic (median number of 25 CTCs) diseases, showing different prognoses. Also, increasing the chemotherapy period resulted in a decrease in the number of captured CTCs from 23 to 7 for the metastatic patient. The MPA-Chip size was only 0.25 cm2 and the throughput of a single chip was 0.5 ml/h, which can be increased by multiple MPA-Chips in parallel. Conclusion The lozenge MPA-Chip presented a novel micropillar geometry for on-chip CTC isolation, detection, and staining, and in the future, the possibilities can be extended to the culture of the CTCs

Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background Detailed, comprehensive, and timely reporting on population health by underlying causes of disability and premature death is crucial to understanding and responding to complex patterns of disease and injury burden over time and across age groups, sexes, and locations. The availability of disease burden estimates can promote evidence-based interventions that enable public health researchers, policy makers, and other professionals to implement strategies that can mitigate diseases. It can also facilitate more rigorous monitoring of progress towards national and international health targets, such as the Sustainable Development Goals. For three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has filled that need. A global network of collaborators contributed to the production of GBD 2021 by providing, reviewing, and analysing all available data. GBD estimates are updated routinely with additional data and refined analytical methods. GBD 2021 presents, for the first time, estimates of health loss due to the COVID-19 pandemic. Methods The GBD 2021 disease and injury burden analysis estimated years lived with disability (YLDs), years of life lost (YLLs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries using 100 983 data sources. Data were extracted from vital registration systems, verbal autopsies, censuses, household surveys, disease-specific registries, health service contact data, and other sources. YLDs were calculated by multiplying cause-age-sex-location-year-specific prevalence of sequelae by their respective disability weights, for each disease and injury. YLLs were calculated by multiplying cause-age-sex-location-year-specific deaths by the standard life expectancy at the age that death occurred. DALYs were calculated by summing YLDs and YLLs. HALE estimates were produced using YLDs per capita and age-specific mortality rates by location, age, sex, year, and cause. 95% uncertainty intervals (UIs) were generated for all final estimates as the 2·5th and 97·5th percentiles values of 500 draws. Uncertainty was propagated at each step of the estimation process. Counts and age-standardised rates were calculated globally, for seven super-regions, 21 regions, 204 countries and territories (including 21 countries with subnational locations), and 811 subnational locations, from 1990 to 2021. Here we report data for 2010 to 2021 to highlight trends in disease burden over the past decade and through the first 2 years of the COVID-19 pandemic. Findings Global DALYs increased from 2·63 billion (95% UI 2·44–2·85) in 2010 to 2·88 billion (2·64–3·15) in 2021 for all causes combined. Much of this increase in the number of DALYs was due to population growth and ageing, as indicated by a decrease in global age-standardised all-cause DALY rates of 14·2% (95% UI 10·7–17·3) between 2010 and 2019. Notably, however, this decrease in rates reversed during the first 2 years of the COVID-19 pandemic, with increases in global age-standardised all-cause DALY rates since 2019 of 4·1% (1·8–6·3) in 2020 and 7·2% (4·7–10·0) in 2021. In 2021, COVID-19 was the leading cause of DALYs globally (212·0 million [198·0–234·5] DALYs), followed by ischaemic heart disease (188·3 million [176·7–198·3]), neonatal disorders (186·3 million [162·3–214·9]), and stroke (160·4 million [148·0–171·7]). However, notable health gains were seen among other leading communicable, maternal, neonatal, and nutritional (CMNN) diseases. Globally between 2010 and 2021, the age-standardised DALY rates for HIV/AIDS decreased by 47·8% (43·3–51·7) and for diarrhoeal diseases decreased by 47·0% (39·9–52·9). Non-communicable diseases contributed 1·73 billion (95% UI 1·54–1·94) DALYs in 2021, with a decrease in age-standardised DALY rates since 2010 of 6·4% (95% UI 3·5–9·5). Between 2010 and 2021, among the 25 leading Level 3 causes, age-standardised DALY rates increased most substantially for anxiety disorders (16·7% [14·0–19·8]), depressive disorders (16·4% [11·9–21·3]), and diabetes (14·0% [10·0–17·4]). Age-standardised DALY rates due to injuries decreased globally by 24·0% (20·7–27·2) between 2010 and 2021, although improvements were not uniform across locations, ages, and sexes. Globally, HALE at birth improved slightly, from 61·3 years (58·6–63·6) in 2010 to 62·2 years (59·4–64·7) in 2021. However, despite this overall increase, HALE decreased by 2·2% (1·6–2·9) between 2019 and 2021. Interpretation Putting the COVID-19 pandemic in the context of a mutually exclusive and collectively exhaustive list of causes of health loss is crucial to understanding its impact and ensuring that health funding and policy address needs at both local and global levels through cost-effective and evidence-based interventions. A global epidemiological transition remains underway. Our findings suggest that prioritising non-communicable disease prevention and treatment policies, as well as strengthening health systems, continues to be crucially important. The progress on reducing the burden of CMNN diseases must not stall; although global trends are improving, the burden of CMNN diseases remains unacceptably high. Evidence-based interventions will help save the lives of young children and mothers and improve the overall health and economic conditions of societies across the world. Governments and multilateral organisations should prioritise pandemic preparedness planning alongside efforts to reduce the burden of diseases and injuries that will strain resources in the coming decades

Development and validation of caregivers' perspectives questionnaire in comatose patients

The caregiver's perspective about care in comatose patients is different among different caregivers, and thus the question is how it is perceived by caregivers. Among the health staff and family members, perspective of caring is obviously different. Thus, the current study was carried out to develop a valid and reliable instrument to assess of caregiver's perspective in comatose patient care. For gathering the data used from the questionnaire consisted of items of Van Manen's hermeneutic phenomenology, then these items combined and validated by content, face and construct validity and by split half and Cronbach a coefficient for reliability. The results showed that the four factors were labeled living with client, efforts for survival, professional conscience and responsibility and respect of human dignity. The perspective of caring of comatose patient questionnaire had 32 items and 4 dimension and showed validity and reliability, but it need to test more and more to multiplication of it's' validity and reliability. © 2013 Asian Network for Scientific Information

Microfluidic-assisted synthesis and modelling of monodispersed magnetic nanocomposites for biomedical applications

Droplet microfluidic was devoted to design and fabricate robust devices in the field of biosensing, tissue engineering, drug delivery, cell encapsulation, cell isolation, and lab-on-a-chip. Chitosan was widely used for different biomedical applications because of its unique characteristics such as antibacterial bioactivities, immune-enhancing influences, and anticancer bioactivities. In this research, a model is used for investigating the formation and size of composite droplets in a microfluidic device. The role of the velocity flow ratio in the composite droplet characteristics such as the generation rate and composite droplet size is described. According to the results, a desirable protocol is developed to control the properties of the composite droplets and to compare the size and rate of the composite droplets in a micro device. Furthermore, the level set laminar two-phase flow approach is exploited for studying the composite droplet-breaking procedure. An experimental procedure is used for validation of the simulation process. Various sizes and geometries of the composite droplets are fabricated to depict a potential in biomedical applications such as bioimaging, biosensing, tissue engineering, drug delivery, cell encapsulation, cancer cell isolation, and lab-on-a-chip

Chitosan/gelatin hydrogel and endometrial stem cells with subsequent atorvastatin injection impact in regenerating spinal cord tissue

Central nervous system trauma can cause loss of functional sensory neurons and motor functions that results in death of neuronal cells and axon degeneration. For this purpose, therapeutic approaches to enhance repair mechanisms spinal cord injury (SCI) is reflected to be a difficult task that requires thoughtful strategy. Hydrogel scaffolds in the presence of stem cells could repair damaged SCI due to their ability to support cellular viability, motility, and differentiation. In this study, we investigated the effectiveness of a biomimetic composite hydrogel of chitosan and gelatin containing endometrial stem cells (EnSCs) as a minimally invasive treatment of SCI in an animal model. Moreover, the simultaneous, effect of intraperitoneal injection of atorvastatin drug was assessed for animal models. From the results, morphological and cell viability studies demonstrated favorable seeding microenvironment and viability in the hydrogel. The transplanted hydrogel containing EnSCs into hemisected SCI rats showed recovery of sensory and motor functions by confirming locomotor activity evaluation using Basso, Beattie, and Bresnahan test. The growth of neuronal cells confirmed with immunohistochemical study. The findings in this study suggested that combination therapy using biomimetic hydrogel seeded with stem cells as well as atorvastatin injection has the potential to heal SCI through neuroinflammation attenuation, improvement of functional recovery, and limit the secondary damages. © 2020 Elsevier B.V