Major Intervention Research Articles

Stable, neuron-specific gene expression in the mouse brain

Gene delivery to, and expression in, the mouse brain is important for understanding gene functions in brain development and disease, or testing gene therapies. Here, we describe an approach to express a transgene in the mouse brain in a cell-type-specific manner. We use stereotaxic injection of a transgene-expressing adeno-associated virus into the mouse brain via the intracerebroventricular route. We demonstrate stable and sustained expression of the transgene in neurons of adult mouse brain, using a reporter gene driven by a neuron-specific promoter. This approach represents a rapid, simple, and cost-effective method for global gene expression in the mouse brain, in a cell-type-specific manner, without major surgical interventions. The described method represents a helpful resource for genetically engineering mice to express a therapeutic gene, for gene therapy studies, or to deliver genetic material for genome editing and developing knockout animal models.

Utility of Cardiac POCUS in the Evaluation of Pediatric Chest Pain in the Emergency Department

Background/Objective:Chest pain in children is rarely caused by a life-threatening pathology. Despite the rarity of potentially life-threatening disease, most children presenting to EDs are evaluated with chest radiographs and laboratory tests without yielding helpful information that significantly changes immediate management. While the utilization of cardiac Point-of-Care Ultrasound (POCUS) by adult emergency physicians has become standard of practice, the data in pediatric emergency departments (PED) is not as robust. This study aims to describe practice patterns in the evaluation of pediatric chest pain presenting in a PED and determine clinical outcomes.
 Methods:We reviewed charts of previously healthy children aged <18 years old who presented to Riley Children’s Hospital from January 2019 to July 2020 with a chief complaint of chest pain. Patients with known medical history, prior evaluations by a pediatric cardiologist, transfers from other hospital with existing workup were excluded. Patient demographics, laboratory tests and imaging ordered while in the ED, electrocardiography (EKG), consults with subspecialties, disposition and follow up plans were analyzed. We categorized clinical significance of PED interventions as minor, moderate, or major.
 Results:Out of three hundred and nineteen patients included in the study, 79.6% (254) received chest radiographs, 93.4% (298) underwent EKG, and 4.1% (13) received cardiac POCUS. The findings of these orders prompted minor interventions in 92.8% (296) of patients, moderateintervention in 4.7% (15) of patients, and major intervention in 2.5% (8) of patients.
 Conclusion and Implications:These results show a lack of use for POCUS in pediatric patients presenting with chest pain while chest radiography is preferred in the ED. Additionally, POCUS did not result in any moderate or major significant clinical outcomes.

Dysregulation of extracellular matrix and Lysyl Oxidase in Ehlers-Danlos syndrome type IV skin fibroblasts

BackgroundEhlers-Danlos syndrome Type IV (aka Vascular Ehlers Danlos, or vEDS) is a dominantly inherited mutation in the Collagen 3A1 gene (COL3A1). The disease is characterized by tissue friability and age-related susceptibility to arterial aneurysm, dissection and rupture as well as uterine and bowl tears. These clinical manifestations result in major surgical intervention and decreased life expectancy. Understanding how mutations in COL3A1 impact the structure and function of the extracellular matrix (ECM) is important to managing the disease and finding treatments.ResultsSkin fibroblasts from vEDS subjects heterozygous for the p.G588S pathogenic variant in the COL3A1 gene and a normal individual were cultured and studied. Proteomics analysis identified dozens of upregulated proteins related to extracellular matrix dysregulation that is characteristic of fibrosis. Gene expression libraries from cultured primary fibroblasts were screened for messenger RNA (mRNA) markers of ECM degradation. The proteomics and targeted gene expression array results were largely consistent with dysregulation of the extracellular matrix in vEDS. The data show upregulation of multiple Collagen proteins and genes, other ECM components, and enzymes related to ECM processing and turn-over. vEDS fibroblasts expressed significantly more cross linked C-Telopeptide of Collagen III (CTXIII) than normal fibroblasts, indicative of Collagen III degradation and turn-over. Further, the expression and activity of Lysyl Oxidase (LOX), an enzyme that initiates covalent cross-linking of soluble collagen and elastin into protease resistant fibers, is elevated in vEDS fibroblasts compared to normal fibroblasts.ConclusionTogether, these findings suggest dysregulated ECM deposition and processing, reminiscent of a state of fibrosis. Therapeutics that target the dysregulated ECM proteins or help replace damaged tissue may improve clinical outcomes.

System identification based structural damage aggravation detection in a large masonry building

System identification is widely used to estimate the dynamic characteristics of structures using either nonparametric or parametric approaches. Parametric system identification constructs mathematical models to estimate dynamic characteristics such as natural frequency, damping ratio, and mode shapes. Also, the same approach can be used to characterize damage if periodic measurements are available. In this paper, we report damage aggravation in a large neoclassical masonry structure using system identification. We took measurements in 2019 and 2023 in the Institute of Engineering, Dean Office building, which was damaged by the 2015 Gorkha, Nepal earthquake. The building is a neoclassical three storied construction with a central courtyard and an extension along the N-S direction. Without major interventions and strengthening, the building is still in use. Using the numerical algorithms for subspace state space system identification (N4SID), vibration frequencies of the structure are identified for both measurements. Also, mode shapes are identified, and damage aggravation is detected using natural frequency and MAC parameters. The first mode frequency along the N-S direction is reduced by 44% and that along the E-W direction is reduced by 1.15%, which indicates a major damage aggravation along the N-S (Y) direction.

Open Defecation Practice and Its Determinants Among Households Owned Toilet Facilities in Gambela Town, South West Ethiopia.

The use of toilet facilities is a major sanitation intervention, as it reduces the spread of diarrheal diseases. In areas where toilets are misused, human excreta may be disposed of in open fields, bushes, and other open places. However, information about the level of utilization of toilet facilities in developing regions of Ethiopia is limited. Therefore, this study aimed to identify open defecation (OD) levels and determinants of OD among household-owned toilets in Gambella town, Ethiopia. A cross-sectional survey was conducted among 561 households in Gambela Town, using systematic random sampling and questionnaires. The level of OD was analyzed using frequency and percentage. The determinants of OD were assessed using binary logistic regression. Variables with a P-value less than .25 in univariable logistic regression were entered into the multivariable logistic regression model, and statistical significance was declared at a P-value less than .05. The model's fit was tested using Hosmer and Lemeshow's goodness of fit. The study found that OD was 47.2% [95% CI: 43.2%-51.4%] among those who owned toilet facilities. The determinants of OD were: occupation of household head [AOR: 5.27, 95% CI: 3.08-9.00], toilet facilities lacking a superstructure [AOR: 2.0, 95% CI: 1.16-3.43], toilet facilities lacking doors [AOR: 3.23, 95% CI: 1.97-5.27], large family size [AOR: 2.16, 95% CI: 1.29-3.60], knowledge of the respondents [AOR: 2.40, 95% CI: 1.50-3.99], and respondents with negative attitude [AOR: 1.76, 95% CI: 1.12-2.74]. Therefore, key stakeholders should focus on improving toilet utilization, considering those factors in their interventions.

Impact Mitigation of Tunnels Maintenance Works on Highway Performance

Major maintenance interventions on highways (e.g., for the safety improvement of tunnels and viaducts) involve the presence of work zones for extended periods of time and along wide sections of the infrastructure. These interventions lead to supply changes, especially a reduction in capacity, causing a decrease in the performance of the transportation system, which users experience with increased traffic congestion and economic losses in terms of productivity. This paper aims to demonstrate that proper traffic management and work zone planning allow for a significant reduction of such impacts. In relation to traffic management, possible solutions consist of diverting traffic flows onto alternative routes (if possible, using primary roads) or keeping them in the remaining lanes along the work zone. In terms of work zone planning, leverage can be applied, on the one hand, through the design of the work zone layout and maintenance scheme and, on the other, through the duration and scheduling of the interventions. The methodology proposed in this paper is based on traffic simulation models in order to assess different maintenance scenarios under varying demand levels (i.e., during the rush hour and off-peak hours, weekdays and weekends, summer and winter months) and vehicular compositions (i.e., percentage of heavy vehicles), with the goal of identifying the scenario that minimizes the impacts on users. Modelling evidence on a real case study of tunnel maintenance interventions on an Italian highway is reported, discussing the policy implications on the basis of quantitative indicators, such as level of service, duration of delays, length of queues, and economic impacts.

Emergy Evaluation of Ecological Engineering for Riparian Restoration in the Upper Reaches of the Yangtze River, China

Complex hydrological regimes and rugged topography in mountainous cities have increasingly compromised urban riparian zones, presenting marked restoration challenges. This study conducted restoration trials along the Jiulongtan riparian zone, located in the upper reaches of the Yangtze River (URYR), China. It featured 2 major ecological engineering interventions: (a) establishing semi-natural meadows and applying braided branched meshes to the riparian slope revetment and (b) constructing littoral woods and managing microtopography and sediment in the floodplain area. Furthermore, emergy evaluation was utilized to gauge the effectiveness of these restoration strategies and to assess the sustainability of the reconstructed riparian ecosystems. The following results were obtained: (a) Both the restored slope revetment (RSR) and restored floodplain (RF) ecosystems achieved a state of performance equilibrium after their implementation, with the former benefiting from renewable energy investments and the latter effectively utilizing local resources; (b) service yield outcomes highlighted significant enhancements in species diversity within the reconstructed ecosystems; plant diversity emerged as the primary contributor to total service yield, recording 3.71 × 10 18 sej/a for the RSR and 5.50 × 10 18 sej/a for the RF; (c) the emergy sustainability index values of 1.98 for the RSR and 5.16 for the RF suggest robust sustainability potential, particularly for the RF, even amid intense environmental stresses. These results affirm the success of the innovative restoration strategies employed for riparian reconstruction in the URYR’s mountainous urban settings, offering valuable insights and reference for future restorative decisions in response to complex hydrological regimes and topography of urban riparian zones, both within the URYR and elsewhere.

Exploring Thoracic Aortic Graft Infection: A Comprehensive Review of Diagnosis and Treatment Options with a Management Strategy Algorithm

As surveillance and the diagnosis of pathology grow, increasing numbers of patients are undergoing major aortic interventions globally. As a result, surgeons and physicians will encounter thoracic aortic graft infections with increasing frequency. These infections are extremely challenging, high‐risk problems to deal with. This article provides a comprehensive overview of the pathogenesis, diagnosis, and management both medical and surgical of this high‐risk complication. We provide proposed diagnostic criteria and suggested algorithm for the management of this important group of patients.

An evaluation of digital intervention for perinatal depression and anxiety: A systematic review

<abstract> <p>Digital intervention has been shown to be helpful in improving perinatal mental health. However, the design characteristics of such interventions have not been systematically reviewed. Considering that a lack of support—especially from a partner—is one of the major contributing factors to perinatal depression and anxiety, it is crucial to determine whether digital interventions have included partner participation. In this review, we systematically examined the design characteristics of digital interventions related to perinatal depression and anxiety and aimed to determine whether partner participation was incorporated as part of the interventions. Based on the PRISMA 2020 guidelines, five databases (PubMed, EBSCO, Cochrane, ProQuest, and Scopus) were searched. Narrative results of design characteristics were developed to provide a framework for the design and evaluation of the studies. A total of 12 intervention studies from China, Sweden, Australia, New Zealand, Singapore, Norway, and the United Kingdom were included. Across all studies, internet cognitive behavioral therapy and mindfulness therapy were overwhelmingly utilized as the major intervention approaches. While all studies reported reduced depressive symptoms after the intervention, only four studies reported subsequent decreased levels of both depressive and anxiety symptoms. Only one study included partner support in the intervention. Cognitive behavioral therapy and mindfulness therapy, two of the most common intervention approaches, were found to be effective in alleviating perinatal depression and anxiety. Partner participation should be prioritized in designing digital interventions to ensure comprehensive and easily accessible social support for persons in need.</p> </abstract>

Advancing health equity in improving breast cancer screening with the use of a mobile mammography bus in marginalised population: quality improvement project

BackgroundBreast cancer, the second leading cause of cancer-related deaths in women in the USA, is effectively treated through early detection and screening. This quality improvement (QI) project aimed to improve...

Solunumsal Yoğun Bakım Ünitesinde İzole Edilen Mikroorganizmalar ve Antibiyotik Direnç Durumlarının Yıllara Göre Değişimi ve Mortaliteye Etkisi

BACKGROUND: Intensive care units (ICU) are multidisciplinary departments where patients with life-threatening diseases, major surgical interventions, respiratory failure, coma condition, hemodynamic insufficiency, and ≥1 organ failure are admitted for relevant diagnoses and treatment. AIM: The present study sought to investigate pathogens causing infections in patients admitted to our respiratory ICU and their antibiotic resistance patterns. MATERİALS and METHOD: The antibiogram results and clinical data of all patient samples submitted between January 1, 2008, and December 31, 2010, were retrospectively reviewed. RESULT: In total, 248 patients with 561 culture results were included in the study. Microbial growth was detected in the following samples: blood, 336 (59.9%); deep tracheal aspirate, 104 (18.6%); urine, 89 (15.9%); wound drain, 12 (2.1%); central venous catheter liquid, 7 (1.3%); phlegm, 10 (1.8%); Foley tip liquid, 1 (0.2%); and pleural effusion, and 1 (0.2%). Rapid growth was most frequently noted in the cultures of coagulase-negative staphylococci (25.3%), Acinetobacter spp. (23.1%), and Escherichia coli (12.6%). STATISTICAL ANALYSIS Descriptive statistics for continuous variables were expressed as means and standard deviations. The intermittent variables were converted into cross-tables and analyzed using Fisher’s exact and Pearson’s chi-square tests. The normal distribution of the study data was assessed using Kolmogorov–Smirnov test. The mean values of the variables were analyzed using Student’s t-test. Bidirectional hypotheses were used, and a p-value of <0.05 was considered statistically significant. The IBM Statistical Package for the Social Sciences Ver. 18.0 for Windows (SPSS Inc., Chicago, IL, USA) software was used for statistical analyses. IN CONCLUSION, the present study revealed microorganisms’ resistance profiles similar to those of other relevant studies. The study provides important insights into the selection of empiric antibiotic therapy for patients admitted in intensive care unit. Keywords: respiratory intensive care unit, intensive care infections, antibiotic resistance, antibiotic susceptibility

Effect of Combination of Temporary Vascular Shunt and Prophylactic Fasciotomy on Limb Salvage after Lower Extremity Arterial Injuries among Yemeni Patients with War-Related Polytrauma

Context and Aim: In cases of severe lower extremity arterial injuries (LEAI), such as those resulting from combatrelated injuries, the preservation of the affected limb is a significant challenge. The combination of a temporary vascular shunt (TVS) and prophylactic fasciotomy (PF) has emerged as a potential approach to improving limb salvage outcomes in these cases. In the context of the war in Yemen, we aimed to assess the effect of combination TVS and PF on limb salvage after LEAI in patients with war-related polytrauma (WRPT). Patients and Methods: A retrospective study was conducted among patients with WRPT at Al Hazm Hospital in Al Jawf Governorate in northeastern Yemen. Cases identified as polytrauma with LEAI in which PF was used comprise the study. These cases were matched to patients, or a control group, injured during the same period having polytrauma with LEAI requiring major vascular intervention but managed without fasciotomy. The primary outcome was surgical amputation. Results: Inclusion criteria were met in 39 cases, 18 (46.2%) had undergone fasciotomy, while the other 21 (53.8%) did not. Both study groups were entirely young (mean age 26.32 ± 5.01 years) males (100%). The overall amputation rate was 17.9% (7 of 39 cases), with 6 (28.57%) cases in the non-fasciotomy group and 1 (5.55%) case in the fasciotomy group. The difference in amputation rate was not statistically significant (p-value, 0.071). Likewise, the mechanism of injury, clinical findings on admission, arterial injuries, and types of surgical procedures were similar in both groups. By contrast, the fasciotomy group had a lower rate of limb infection than their non-fasciotomy counterpart (38.1% vs. 5.6%, respectively). The mortality rate in the hospital was 5.1% (2 of 39 cases), and all of them did not undergo fasciotomies. Conclusion: The combination of TVS and PF was associated with significantly improved limb infection. While statistically unproven, this combination may also enhance limb salvage. Therefore, it should be performed in cases of WRPT.

Crop Intensification through Short Duration Stress-Tolerant Rice Varieties with Green Gram for Fostering Agricultural Resilience and Sustainability

Rice stands as a critical cornerstone in the pursuit of food security due to its unparalleled significance as a staple crop for billions of people worldwide. Rice in India, is cultivated within diverse cropping systems that harness the nation's rich agro-climatic variations. Eastern India has emerged as a significant contributor to the country's overall rice production. Nevertheless, most of the existing cropping systems of rice in this region suffer from some drawbacks, primarily due to monoculture practices and limited crop diversity. An experiment was conducted in the Eastern Indian State of Odisha to evaluate the efficiency and profitability of promoting a rice-green gram-rice cropping system. The experiment consists of two major interrelated interventions viz., awareness regarding short-duration stress-tolerant rice varieties (STRV) and the introduction of the new crop for higher economic returns. Varietal awareness programs were organized before the onset of the wet season of 2020 and the potential benefits of cultivating STRV over the popular traditional cultivars were communicated to the target farmers, besides advocating the rice-green gram-rice cropping system. The study employed a field experiment design to compare the performance of existing and new cropping systems. The impact evaluation was carried out after recording the comments of the farmers followed by a thorough comparison between the new and existing cropping systems. The available evidence suggests that the introduced short-duration STRVs are better than the already existing varieties and have the potential to change the cropping system of the region. The most desirable trait of these varieties as reported by the farmers is their short maturity duration. The results do unequivocally demonstrate the superior performance of the new cropping system over the existing system in terms of crop yield, diversification, and profitability. This remarkably underscores the potential of the new system to address food security challenges and enhance agricultural productivity.

Anthropogenic Hazards and Their Impact Upon the Historical Cultural Landscape in Roșia Montană Area

Anthropogenic Hazards and Their Impact upon the Historical Cultural Landscape in Roșia Montană Area. The cultural landscape is a result of the continuous human actions of satisfying the communities’ various needs and the response of the natural system, in its attempt to balance its components in relation to the modelling factor - the human society. Thus, the cultural landscape displays the imprint of the infinite possibilities of the human and natural joint manifestation, sometimes hazards bringing their own contribution to the shaping of the cultural landscape. Hazards, whether natural or anthropogenic, are unforeseen phenomena in terms of space or time of their manifestation, and most often have considerable negative consequences. In particular, anthropogenic hazards, which are directly or indirectly related to human activities, appear mainly as a manifestation of the resilience of natural elements in the cultural landscape, as a complex system. Thus, major interventions, such as mining in Roșia Montană area (an activity that had been lasting for over 2000 years) in relation to the unpredictable evolution of the social, economic, technological and political context (on local, national and global level) have favoured the manifestation of some unforeseen events with a negative connotation such as: complex pollution, depreciation of the living standards (in Roșia Montană area mostly due to the cessation of mining activities), demographic aging, etc. The complex analysis of these implications in the above-mentioned area allows us to outline an eloquent assessment of the present state of the local cultural landscape and to identify the opportunities of systemic resilience. These include: the awareness of the planning, protection and conservation of the local historical cultural landscape as a primary need, restoration of the cultural landscape (through the aesthetic rehabilitation of degraded cultural elements), the implementation of projects that target the sustainable development of Roșia Montană, as a source of identity and sustainable development, the tourism conversion of activities, etc. Keywords: Roșia Montană, cultural landscape, historical cultural landscape, anthropogenic hazards, mining, gold deposits.

Compare Three Types of Surgery for Meniscal Tears

Meniscus injuries, often associated with sports, have become a growing concern because of their potential to affect patients’ knee joints and, thus, People’s Daily lives. A meniscal tear is a half-moon-shaped fibrous cartilage structure in the knee joint. This article explores the meniscus’s complex anatomical structure and biochemistry, emphasizing its critical importance in maintaining optimal knee function. Our discussion extends to modern diagnostic procedures, particularly emphasizing the direct visualization capabilities of non-invasive magnetic resonance imaging (MRI) and arthroscopy. In addition, this paper lists three major surgical interventions for meniscus injuries: Meniscus repair, which aims to preserve the natural meniscus; Meniscectomy, the removal of the damaged meniscus; and Meniscus replacement using biological grafts or innovative synthetic materials. While meniscectomy can provide quick relief from symptoms, it carries the potential threat of diseases such as osteoarthritis in the long run. In contrast, meniscus repair and replacement strategies are longer-lasting treatment options, although postoperative recovery times and the complexity of the procedure vary.

A Study on Failure Rate, Reliability, and Collection Efficiency Trend of Bag Filters in a Cement Plant

This thesis presents a comprehensive study on the failure rate, reliability, and collection efficiency trends of bag filters in a cement plant over 15 years. Bag filters are vital pollution control equipment used in various industries, including cement plants, to maintain environmental compliance. Understanding their performance and failure patterns is crucial to ensure efficient and reliable operation while adhering to stringent pollution control standards. The research findings reveal that the failure rate trend of bag filters closely follows the bathtub curve, with an initial high failure rate, a period of lower failures, and a subsequent increase in failures as the equipment nears the end of its life cycle. Reliability trends align with Madhab's Hat curve, exhibiting higher reliability during the first 10 to 12 years of operation, followed by a decline in reliability. The collection efficiency of bag filters declines as the equipment ages, with the efficiency decreasing from 99.998% in the early years to 95.05% in the 15th year. This emphasizes the importance of maintenance and retrofitting for older dust collection equipment to maintain high collection efficiency. The study concludes that the typical life span of bag filters ranges from 10 to 15 years, after which major maintenance interventions are necessary to minimize failure rates. The research provides valuable insights for maintenance engineers, design engineers, and reliability engineers, enabling them to improve the performance of pollution control equipment, such as bag filters, reverse air bag houses (RABH), and electrostatic precipitators (ESP), to meet the pollution control standards set by regulatory authorities.

INSTITUTIONAL INNOVATIONS IN COMMERCIALIZATION OF OKRA

The commercialization of okra in Tapi’s agricultural scenario is primarily the result of institutional interventions carried out through participation over the previous forty years, with a primary concentration on production followed marketing interventions. It has been observed that these interventions are successful in changing the agricultural sector of the region from parochial paddy cultivation to commercial okra farming. In current scenario, the major marketing-centric institutional interventions of the export promoting agencies have highlighted the relevance of institutional innovations in the promotion of okra in the region. A comparative gain of Rs. 37,475 per hectare has been reported for growers following export-oriented okra production. The study has shown the potential benefits of comprehensive institutional interventions persuaded by the export agencies in Tapi. A comparative analysis of marketing has revealed that marketing channel of okra via. exporting agency is the most efficient. The benefits of informal community participation under appropriate supervision and leadership have been shown by the study.

Massage-like stroking produces analgesia in mice

Chronic pain treatment remains a major challenge and pharmacological interventions are associated with important side effects. Manual medicine treatments such as massage, acupuncture, manipulation of the fascial system (MFS), and osteopathic manipulative treatments produce pain relief in humans, but the underlying mechanism is poorly understood limiting leverage and optimization of manual medicine techniques as safe pain therapy. To decipher the physiological mechanisms of manipulative medicine treatments, we have established a preclinical model. Here, we established a murine model of massage-like stroking (MLS)-induced analgesia. We characterized that the analgesia effects were present in both sexes, and were independent of the experimenters, handling, consciousness, and opioid receptors. MLS alleviates thermal pain in naive mice and postoperative pain hypersensitivity. This novel model will allow discovery of the physiological mechanisms involved in MLS-induced analgesia and identification of new therapeutic strategies.

MULTILEVEL LIFESTYLE INTERVENTIONS ARE NEEDED TO IMPROVE DIABETES SELF-MANAGEMENT IN OLDER ADULTS

Abstract Type 2 diabetes (T2D) is a major public health concern in older adults. Physical activity (PA) and healthy eating (HE) are two major lifestyle intervention strategies in diabetes self-management for controlling glucose levels, preventing complications, and improving functionality and quality of life. This qualitative study aimed to explore perceived factors influencing PA and HE among predominately Latino older adults with T2D ((age=70.5±4.8; Latinos=73.3%). We conducted semi-structured interviews with 15 community dwelling older adults with T2D at the end of a 12-week pre- and post- study assessing self-monitoring on lifestyles and health outcomes. All interviews were recorded and transcribed. Two researchers analyzed the data independently using a combination of deductive and inductive thematical analysis. Codes were categorized into five themes based on the socio-ecological framework, and sub-themes were identified. The themes included five levels of factors: 1) individual (e.g., knowledge, self-efficacy, self-monitoring, perceived benefits and threats, health status,); 2) interpersonal (e.g., family, friend, health provider); 3) organizational (e.g., availability of physical activity equipment in senior apartments); 4) environment (e.g., culture norms); and 5) policy factors (e.g., health provider, retirement). The factors in one level could influence the factors in another level. Most current lifestyle interventions focus on individual level, and multilevel lifestyle interventions to promote healthy lifestyles, and improve health, independence, and quality of life in older adults with T2D are warranted. The input of additional stakeholders such as family members and community staff need to be accounted when designing multilevel intervention in older adults with T2D.

Whole blood stimulation as a tool for studying the human immune system.

The human immune system is best accessible via tissues and organs not requiring major surgical intervention, such as blood. In many circumstances, circulating immune cells correlate with an individual's health state and give insight into physiological and pathophysiological processes. Stimulating whole blood ex vivo is a powerful tool to investigate immune responses. In the context of clinical research, the applications of whole blood stimulation include host immunity, disease characterization, diagnosis, treatment, and drug development. Here, we summarize different setups and readouts of whole blood assays and discuss applications for preclinical research and clinical practice. Finally, we propose combining whole blood stimulation with high-throughput technologies, such as single-cell RNA-sequencing, to comprehensively analyze the human immune system for the identification of biomarkers, therapeutic interventions as well as companion diagnostics.