Environmental Stimulation Research Articles

Cognitive Reserve proxies for individuals with intellectual disabilities: a Scoping Review

AbstractBackgroundDementia in people with Intellectual Disability (ID) has a prevalence three times greater (Strydom et al., 2007) and with an earlier onset (Dodd et al., 2015) than in the general population. Despite the fact that virtually all adults with ID display neuropathology consistent with dementia by the age of 40, many of them never show the clinical symptoms (Strydom et al., 2009): there is no linear link between degree of brain damage and severity of the symptomatology (Arvio & Bjelogrlic‐Laakso, 2021). This discrepancy could be attributed to a difference in Cognitive Reserve (CR, Stern, 2009). However, CR has never been systematically studied specifically in relation to ID. To fill this gap, we aimed to identify potential indicators (“proxies”) of CR specifically relevant for people with ID to be included in future instruments. Indeed, activities potentially promoting and enhancing CR in people with ID may not overlap with those considered by the instruments for the general population (see CRIq, Nucci et al., 2012).MethodA Scoping Review was conducted in PubMed and Scopus. N = 1239 potentially relevant papers were identified, 104 papers were assessed for eligibility and 17 studies matched our inclusion criteria.ResultWe consider as proxies of CR all lifestyle factors and life experiences proven in past studies to be positively correlated with the cognitive performance or with the everyday functioning of adults with ID, even if not explicitly labeled as proxies of CR. Some proxies found are partly overlapping with the ones used to quantify CR in the general population: Education, Occupation, Leisure and Physical activity. Yet, others are uniquely suitable for the population with ID: Type of schooling, Parental educational level, Environmental stimulation and Living place. Those should be incorporated within the instruments developed and validated in the future to assess the CR of people with ID.ConclusionThis Review is the first step toward the development of the first instrument to measure CR in people with ID. The hope is that it will be integrated among the instruments routine used in the clinical practice and assure people with ID an early and accurate diagnosis of dementia.

Abstract C064: Combination of D3L-002, an anti-TIGIT/PVRIG bispecific antibody, with D3S-001, a KRAS G12C inhibitor, transformed tumor microenvironment from “cold” to “hot” and achieved durable tumor remission in preclinical models

Abstract KRAS G12C inhibitors have demonstrated encouraging clinical benefit in patients with solid tumors harboring KRAS G12C mutation. However, the overall response rate and duration of response remain to be improved. Though combining KRAS G12C inhibitors with anti-PD-1 antibodies showed enhanced preclinical efficacy, clinical benefit for this regimen was compromised by treatment-related toxicities. While the mechanisms underlining these toxicities are being actively investigated, combination strategies incorporating other immunotherapies into KRAS G12C inhibition may provide an alternative to anti-PD-1 combination. We have discovered a new bispecific antibody (BsAb), D3L-002, targeting the TIGIT and PVRIG immune checkpoint molecules that are expressed on activated T and NK cells and mediate inhibitory signaling to counteract the immune stimulatory DNAM-1 pathway. To assess the combination effect of D3L-002 with KRAS G12C inhibitors, the anti-tumor efficacies of KRAS G12C inhibitor D3S-001, a murine surrogate anti-TIGITxPVRIG BsAb (mTxP BsAb), a murine anti-PD-1 antibody (mPD-1 Ab), the combination of D3S-001 with mTxP BsAb and with mPD-1 Ab were evaluated in CT-26 KRAS G12C syngeneic mouse tumor models. Tumor microenvironment (TME) profiling was analyzed by flow cytometry, immunohistology and single cell sequencing. In this study, D3S-001 monotherapy inhibited tumor growth with a 50% complete remission (CR) rate. While mTxP BsAb alone was not effective in this immune “cold” model, combination of D3S-001 with mTxP BsAb resulted in a 70% CR rate, comparable to that of the combination of D3S-001 with the mPD-1 Ab. TME profiling indicated that D3S-001 remodeled the TME from “cold” to “hot” by reducing M2 macrophages and MDSCs while increasing T cells in the tumor. Interestingly, D3S-001 treatment led to increased expression of DNAM-1 on T cells, which has been implicated in augmenting T cell sensitivity towards environmental stimulation. The expression of TIGIT and PD-1 was also upregulated on T cells after D3S-001 treatment, correlating with enhanced T cell activation and anti-tumor efficacy in the combination group of mTxP BsAb and D3S-001 or mPD-1 Ab and D3S-001, respectively. In single cell analysis, mTxP BsAb demonstrated a distinctive effect in regulating immune suppressive Treg population from that of the mPD-1 Ab. While Treg population was increased in D3S-001 or the combination of D3S-001 with mPD-1 Ab group, it was decreased in mTxP BsAb monotherapy or D3S-001 and mTxP BsAb combination group. Collectively, these data showed that D3S-L002’s surrogate mTxP BsAb synergized with D3S-001 in achieving enhanced and durable anti-tumor effect in KRAS G12C-mutant tumors. The combination treatment transformed TME from “cold” to “hot” and inhibited Treg population. These results provide a strong rationale for combining D3L-002 with D3S-001 in clinic trials, which may lead to an alternative treatment option, with differentiated mechanisms and potentially better tolerability, from current strategy in combining anti-PD-1 antibodies with KRAS G12C inhibitors. Citation Format: George Chen, Jing Zhang, Haopeng Rui, Xiaofeng Yang, Tienan Wang. Combination of D3L-002, an anti-TIGIT/PVRIG bispecific antibody, with D3S-001, a KRAS G12C inhibitor, transformed tumor microenvironment from “cold” to “hot” and achieved durable tumor remission in preclinical models [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C064.

Stimuli‐responsive colorimetric polydiacetylene sensor in polar organic solvent

AbstractPolydiacetylene (PDA) has been actively employed as sensing vehicles owing to its unique colorimetric feature upon environmental stimulation. Here, blue phase PDA has been constructed by topological polymerization of commercial diacetylene acid (DA) noncovalently modified by guest amines. Specifically, PDA including 1‐naphthylmethylamine noncovalently bonded on both sides exhibits long‐term stability in polar organic solvents. The stability of PDA depended upon both the structures of the DA and the guest molecule, underscoring a stabilizing mechanism dominated by noncovalent bonding and strong π–π interaction. Accordingly, the blue phase PDA shows a colorimetric response from blue to red upon exposure to stimuli influencing noncovalent bonding and π–π interaction, such as elevated temperature, the existence of acid or alkali at concentrations as low as 50 ppm. Therefore, the PDA developed in this study has the potential of serving as a colorimetric sensor for detecting subtle environment changes and especially for measuring the quality of polar organic solvents recovered from industrial effluent.

Motivation and Academic Performance of Secondary Students in Science: A Correlational Study

Motivation theories have suggested that motivation and academic performance are positively related. While many studies worldwide have explored this relationship, investigation in the Philippine educational setting remains scarce. Hence, this study described the levels of students’ motivation towards learning and academic performance in science and determined whether a significant relationship existed between these variables. Employing a correlational research design, this study surveyed 318 secondary students in a private, diocesan school in Davao del Norte, Philippines. Mean, standard deviation, and Pearson r were used to analyze the data. Results showed students’ motivation towards learning was generally high, and their academic performance was very satisfactory. Among the factors considered for motivation, only performance goal posted a moderate level, while other aspects, such as achievement goal, active learning strategies, learning environment stimulations, science learning value, and self-efficacy, registered high levels. Furthermore, this study revealed the students’ motivation towards learning and academic performance were positively and significantly correlated. While this study already found high motivation and very satisfactory academic performance among students, the researchers still recommend raising them to very high and outstanding levels, respectively. Further research on this topic with a more representative sample is highly recommended. Using other constructs to relate to any of the variables is also encouraged

EGR1 Mediated Reduction of Fibroblast Secreted-TGF-β1 Exacerbated CD8+ T Cell Inflammation and Migration in Vitiligo.

Vitiligo is a T cell-mediated depigment skin disease caused by the complex interplay between melanocyte dysfunction, environmental stimulation, and dysregulated immune signals. Transforming growth factor-β1 (TGF-β1), which typically derives from regulatory T cells, has long been identified at low levels in the peripheral system of vitiligo patients. Here, through RNA-sequencing and transcription factor enrichment, we revealed that in response to CD8+ T cell-secreted interferon-gamma (IFN-γ), stromal fibroblast downregulates early growth response 1 (EGR1) activity, leading to TGF-β1 deficiency. The defective immune regulation loop further exacerbated local CD8+ T cell inflammation and promoted inflammatory cell migration in vitiligo. Thus, fibroblast-derived TGF-β1 plays an important stromal signal in vitiligo pathogenesis.

Going to the office - What’s in it for the dog?

ABSTRACT Benefits and challenges of dogs being present at the office were analyzed from three perspectives: the company view, the dog owner (employee) and the dog view. For companies, office dogs may serve as a branding symbol, leading to higher employee satisfaction and productivity, increased stress resilience and fewer turnover intentions. Yet, companies need to apply pet policies, risk management strategies and mitigate nuisance such as barking, loose fur or excrement. Additional breaks to walk the dogs are required and other employees or customers may be irritated. Employees take advantage of stress reduction, social support, higher job satisfaction, not having to leave their animal at home. Still, an office dog is an added responsibility in terms well-being, safety, distraction from work and emotional involvement. Although the animal perspective has not yet been scientifically addressed, we propose potential benefits such as less separation distress by having the owner nearby, higher social engagement and additional walks during breaks. Challenges for dogs may involve unwanted attention, aversive environmental stimulation, being restrained via leash or crate, irritation caused by conspecifics, emotional contagion or individual requirements.

Emerging Research Advancements to Overcome the Peach Spring Frost

The phenomena of global warming has led to an increase in the average air temperature in temperate climates. Springtime frost damage is becoming more common, and after a period of dormancy, damage to buds, blooms, and developing fruits is greater significant than damage from low winter temperatures. Peaches are a crucial crop among moderate fruits. Spring frost damage in peaches can have a negative effect on crop growth, yield, and quality. It is noteworthy that these plants have evolved defenses against spring frost damage while being exposed to a variety of low temperatures in the early spring. In this current review, recent research advancements on spring frost damage avoidance in peaches were deliberated. Additionally, adaptive mechanisms of peach, such as deacclimation and reacclimation, were emphasized. Moreover, the emerging advancements using various omics approaches revealed the peach physiology and molecular mechanisms comprehensively. Furthermore, the use of chemical products and understanding the spring frost mechanisms through the use of environmental chamber temperature stimulation and infrared thermography studies were also discussed. This review is essential groundwork and paves the way to derive and design future research for agronomists and horticulturalists to overcome the challenges of spring frost damage avoidance and crop management in these circumstances.

Time-motion observations to characterize the developmental environment in a paediatric post-acute care hospital.

Chronically hospitalized children are at risk for neurodevelopmental delay, compounded by restricted social interactions, movement and environmental stimulation. We measured patients' movements and interactions to characterize developmentally relevant aspects of our inpatient environment and identify opportunities for developmental enrichment. As part of a quality improvement initiative to inform neurodevelopmental programming for children with medical complexity at our paediatric post-acute care specialty hospital, we conducted >232 hours of time-motion observations. Trained observers followed 0- to 5-year-old inpatients from 7am to 7pm on weekdays, categorizing observations within five domains: Where, With, Position, State and Environment. Observations were collected continuously utilizing REDCap on iPads. A change in any domain initiated a new observation. Patients were median 1year and 8months of age (range 2months to 3years 9months) with a median length of hospitalization of 514 days (range 66-1298). In total, 2636 unique observations (or median 134 observations per patient-day [range 95-210]) were collected. Patients left their rooms up to 4 times per day for median 1h and 34 min (range 41 min to 4h:30 min). Patients spent 4h:6min (2h:57 min to 6h:30 min) interacting with someone and 3h:51 min (57 min to 6h:36 min) out of bed each day. Patients were simultaneously out of their beds, interacting with someone and awake for 2h:21 min (51 min to 4h:19 min) each day. Despite a care model prioritizing time out of bed and social interaction, time-motion observations indicate patients spent many of their waking hours in bed and alone. Quantifying our inpatients developmental opportunities will inform neurodevelopmental programming initiatives.

Exosomal miRNA analysis provides new insights into exposure to nanoplastics and okadaic acid

As an emerging environmental pollutant, nanoplastics (NPs) have attracted wide attention in terms of their impact on the ecological environment and human health. Currently, researches on the cytotoxicity of NPs mainly focus on oxidative stress, damage to the cell membrane and organelles, induction of immune response and genotoxicity. Okadaic acid (OA) is the main component of diarrheal shellfish toxin. Based on the previous combined toxicity exploration of polystyrene (PS) NPs and (OA) to human gastric adenocarcinoma (AGS) cells, cell-derived exosomes were extracted and exosomal miRNA profiles were analyzed for the first time in this study. The results showed that the composition of miRNAs varied after the exposure of NPs and OA. Specifically, the expression of miR-1-3p in both PS-Exo and PS-OA-Exo was significantly reduced. And the expression of miR-1248 was upregulated most significantly by comparing the DE miRNAs between PS-Exo and PS-OA-Exo. MiR-1-3p and miR-1248 may be the key genes for the combined toxicity of NPs and OA. After analysis, we found that both the decreased expression of miR-1-3p and the increased expression of miR-1248 can increase the expression of FN1 and affect DNA replication, which was surprisingly consistent with the results of our previous cytotoxicity studies. Since exosomal miRNAs are selectively encapsulated by donor cell, we speculate that the changes of exosomal miRNAs may due to the synchronous changes of intracellular environment and the downregulation of intracellular FN1 may be attributed to decreased expression of miR-1-3p and increased expression of miR-1248 in donor cells. Accordingly, we come to the conclusion that the changes of miRNAs in the exosomes derived from AGS cells after environmental stimulation could reflect the biological effects of donor cells.

Thermal decomposition characteristics and thermal safety performance evaluation of HAN-based propellant under different external environmental stimulations

This research aims to investigate thermal characteristics and assess thermal hazards of hydroxylamine nitrate (HAN)-based liquid propellant using a combination of accelerating rate calorimeter and high-pressure differential scanning calorimetry. Adiabatic experiments revealed that the exothermic reaction initiated at 115.7 °C and a rise sharply was at 128.4 °C with a maximum self-heating rate of 164.3 °C/min and the exothermic event was accompanied by a pressure rise of 3.7 bar in 0.03s. The corrected values of adiabatic temperature rise and time to maximum rate were 605.6 °C and 1.46 min, which confirms the vulnerability of the propellant to undergo a catastrophic explosion. To prevent thermal loss prevention accidents, time to maximum rate was obtained as 24 h under 111.3 °C. The apparent activation energy calculated decreased greatly with the increase of storage temperature from 25 °C to 45 °C, and so did the thermal explosion temperature (Tb) and self-accelerating decomposition temperature (TSADT). Additionally, the linear relationship between Ea and T was E = 991.7–2.7904T. The reliability of TSADT prediction was validated through slow cook-off test. Furthermore, the propellant exhibited more violent thermal decomposition under high pressure, resulting in a higher peak power. The thermokinetic parameters related to this phenomenon were identified, specifically at pressure of 4.0 MPa.

Effect of different suspension moxibustion methods on syndrome characteristics of rats with rheumatoid arthritis of heat bi syndrome based on "moxibustion can be used for heat syndrome"

To observe the effects of different suspension moxibustion methods on the syndrome characteristics and inflammatory factors of rats with rheumatoid arthritis (RA) of heat bi syndrome and to prove the concept of "moxibustion can be used for heat syndrome". Among seventy Wistar rats, 12 rats were randomly selected as a normal group, and the remaining rats were induced by collagen combined with wind, dampness, and heat environmental stimulation to establish the RA model of heat bi syndrome. Forty-eight rats with successful model establishment were further randomly divided into a model group and three moxibustion groups (mild moxibustion group, rotating moxibustion group and sparrow-pecking moxibustion group), with 12 rats in each group. The acupoints "Quchi" (LI 11), "Dazhui" (GV 14) and ashi point were used in all moxibustion groups, with mild moxibustion, rotating moxibustion, and sparrow-pecking moxibustion intervention given respectively, each acupoint was treated with moxibustion for 10 min a day, and 6 days were considered one course of treatment, with a total of three courses. After the intervention, the arthritis index (AI), the Evans blue (EB) extravasated volume in the soft tissue of the right hind paw, and the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-10 in the serum were measured by ELISA in each group. The volume of the bilateral hind paw was measured; the infrared thermal imaging was collected to analyze the temperature of the plantar area of the bilateral foot pads, and the reaction time of plantar heat pain was calculated before and after modeling, as well as after the 1st, 2nd and 3rd courses of interrention. The ankle dorsiflexion angle of the right hind foot was also measured before and after modeling, as well as after the intervention. After modeling, compared with the normal group, the rats in the model group had more high-temperature areas in the bilateral hind limbs, abnormal AI score, abnormal bilateral hind paw volume, abnormal temperature of the plantar area of the bilateral foot pads, abnormal foot pain response time, abnormal right hind ankle dorsiflexion angle, abnormal right hind paw soft tissue EB extravasation, and abnormal serum TNF-α and IL-10 levels (P<0.01, P<0.05). After the intervention, compared with the model group, the rats in each moxibustion group had decreased or disappeared high-temperature areas in the bilateral hind limbs, EB extravasated volume in the soft tissue of the right hind paw was reduced (P<0.05), and the right ankle dorsiflexion angle was increased (P<0.05), serum level of TNF-α was reduced, and level of IL-10 increased (P<0.05); the AI scores in the mild moxibustion group and the sparrow-pecking moxibustion group was decreased (P<0.01, P<0.05). After the 1st, 2nd and 3rd courses of intervention, compared with the model group, the bilateral hind paw volume of rats in each moxibustion group was decreased (P<0.05, P<0.01), and plantar heat pain reaction time was increased (P<0.05). After the 2nd course and the 3rd course of intervention, the temperature of the right hind paw pad area was decreased in each moribustion group (P<0.05); after the 3rd courses of intervention, the temperature of the left hind paw pad area was decreased in the mild moxibustion group (P<0.05). Suspension moxibustion could adjust the serum levels of TNF-α and IL-10 to improve the syndrome characteristics of RA rats of heat bi syndrome, such as joint redness, swelling, heat, pain and activity restriction. The effect of mild moxibustion is the most prominent. The findings could provide scientific basis for "moxibustion can be used for heat syndrome".

Single-cell RNA sequencing in dissecting microenvironment of age-related macular degeneration: Challenges and perspectives.

Age-related macular degeneration (AMD) is the leading cause of blindness in individuals over the age of 50 years, yet its etiology and pathogenesis largely remain uncovered. Single-cell RNA sequencing (scRNA-seq) technologies are recently developed and have a number of advantages over conventional bulk RNA sequencing techniques in uncovering the heterogeneity of complex microenvironments containing numerous cell types and cell communications during various biological processes. In this review, we summarize the latest discovered cellular components and regulatory mechanisms during AMD development revealed by scRNA-seq. In addition, we discuss the main challenges and future directions in exploring the pathophysiology of AMD equipped with single-cell technologies. Our review underscores the importance of multimodal single-cell platforms (such as single-cell spatiotemporal multi-omics and single-cell exosome omics) as new approaches for basic and clinical AMD research in identifying biomarker, characterizing cellular responses to drug treatment and environmental stimulation.

Systematic review: Factors influencing creativity in the design discipline and assessment criteria

Using psychological instrument to measure creativity is getting popular in design research. However, unlike quantifying general creativity using divergent thinking, the complexity and interdisciplinarity of the design discipline have made it difficult to explore research on design creativity. Therefore, to better quantify and measure design creativity, 31 relevant studies were retrieved by Google Scholar and the University of London Common Research in this article. This study summarizes the factors that influence design creativity in different design disciplines, the rules for setting the internal dimensions, and the valid instruments for measuring design creativity. The factors affecting design creativity can be divided into internal factors (aesthetic, spatial ability, and ambiguity tolerance) and external factors (environment and visual stimulation). Among these factors, different instruments and evaluation criteria considerably impact the result, while the measurement of design creativity is still not mature enough. A single scale evaluation or creative task evaluation cannot comprehensively evaluate the design creativity, which consists of aesthetic, functional, and technical aspects. In addition, the reference value of ordinary creativity remains to be further discussed in design. Under some professional design fields, the effect of widely recognized factors closely related to creativity, such as divergent thinking, imagination, and personality, is insignificant.

The impact of floatation therapy on body image and anxiety in anorexia nervosa: a randomised clinical efficacy trial

Body image disturbance and anxiety are core features of anorexia nervosa (AN), a psychiatric disorder with one of the highest mortality rates. This study examined the efficacy of a novel non-pharmacological treatment, floatation-REST (Reduced Environmental Stimulation Therapy) on body image disturbance and anxiety in inpatients with AN. This parallel group randomised controlled trial compared floatation-REST vs. care as usual in women and girls hospitalised for treatment of AN in Tulsa, Oklahoma, USA. Participants were randomised on a 2:1 ratio to receive eight, twice-weekly, 60-min floatation-REST sessions for 4 weeks, in addition to care as usual, or to receive care as usual. The primary outcome was the average change in body dissatisfaction from pre- to post-float as measured by the Photographic FigureRating Scale. The secondary outcome was the average change in anxiety from pre- to post-float as measured by the state version of the State Trait Anxiety Inventory. Longitudinal effects of floatation-REST on body dissatisfaction were also examined. All analyses were conducted using the intention-to-treat principle. Planned linear mixed models tested the effect of floatation-REST vs. care as usual. The trial was preregistered (clinicaltrials.govNCT03610451). Between March 16, 2018 and February 25, 2021, 133 participants were screened for eligibility, and 86 were consented. Eighteen were excluded after consent, for a final randomisation sample of 68 participants (45 floatation-REST; 23 care as usual). There were two session by condition interactions on body dissatisfaction (p=0.00026) and state anxiety (p<0.0001), such that the floatation-REST group exhibited acute (i.e., pre- to post-session) reductions in body dissatisfaction (floatation-REST group mean change (Δm)=-0.43; 95% CI-0.56 to-0.30, p<0.0001, Cohen's d=0.23), and acute reductions in anxiety (floatation-REST group Δm=-15.75; 95% CI-17.95 to-13.56, p<0.0001, Cohen's d=1.52); however, the care as usual group exhibited no significant changes. With regard to longitudinal results, there was a significant time by treatment interaction between baseline and immediately post intervention (p=0.012) and baseline and six-month follow up (p=0.0019). At immediately post intervention, there was a trending reduction in body dissatisfaction for the floatation-REST group (Δm=-0.41, 95% CI-0.86 to 0.03, p=0.068) and care as usual group (Δm=0.61; 95% CI-0.04 to 1.27, p=0.070). At six-months post-intervention, the floatation-REST group exhibited lower body dissatisfaction (Δm=-0.91; 95% CI-1.37 to-0.45, p=0.0020, Cohen's d=0.53) whereas the care as usual group reported no change in body dissatisfaction (Δm=0.35; 95% CI-0.28 to 0.98, p=0.96) relative to baseline. There were no adverse events related to the trial during the study. Our findings suggest that Floatation-REST decreased body dissatisfaction compared to care as usual acutely after each float session and at six-month follow-up. Floatation-REST has potential utility for the treatment of body image disturbance and anxiety in AN. These results may be limited by some generalisability concerns given the recruitment of a modest sample receiving inpatient treatment at a single site. The William K. Warren Foundation.

Effect of microserum environment stimulation on extraction and biological function of colorectal cancer stem cells

Background3D cancer stem cell (CSC) cultures are widely used as in vitro tumor models. In this study, we determined the effects of enriching HCT116 tumor spheres initially cultured in serum-free medium with different concentrations of serum, focusing on the effect of microserum environment stimulation on extraction and biological function of colorectal cancer stem cells (CCSCs).MethodsCCSCs were enriched in standard serum-free medium and serum-free medium with different concentrations of serum for 1 week. The expression of CSC-associated markers in CCSCs, and the presence and relative proportion of CSCs (CD133/CD44 cell sorting) were then determined to elucidate the effect of the microserum environment on the preservation of CSC-related features. Further, the tumorigenic capacity of CCSCs was evaluated in an immunodeficiency mouse model.ResultsOur data indicated that a significantly greater number of spheres with a greater size range and high viability without drastic alteration in biological and structural features, which maintained self‐renewal potential after sequential passages were formed after serum supplementation. Real-time analysis showed that both serum spheres and serum-free spheres displayed similar expression patterns for key stemness genes. Serum spheres showed higher expression of the CSC surface markers CD133 and CD44 than did CSCs spheres cultured in serum-free medium. Adherent cultures in complete medium could adapt to the serum-containing microenvironment faster and showed higher proliferation ability. The addition of serum induced EMT and promoted the migration and invasion of serum globular cells. Compared with serum-free cells and adherent cells, serum spheres showed higher tumor initiation ability.ConclusionsMicroserum environment stimulation could be an effective strategy for reliable enrichment of intact CCSCs, and a more efficient CSC enrichment method.

New evidence of trends in cognitive function among middle-aged and older adults in China, 2011-2018: an age-period-cohort analysis

BackgroundIncreasing evidence from high-income countries suggests the risk of cognitive impairment has been declining recently. However, related studies in China have rarely been done, and the results are inconsistent. We analyze the trends in cognitive function among middle-aged and older adults in China between 2011 and 2018.MethodsWe used data from four waves of the China Health and Retirement Longitudinal Study (CHARLS), including 48918 individuals aged 45 years and older. Cognitive function was assessed using the CHARLS cognitive measures containing episodic memory, orientation, attention, and visuospatial abilities. The hierarchical age-period-cohort (APC) model was used to quantify the separate age, period, and cohort effects on trends in cognitive function.ResultsThe study sample’s ages ranged from 45 to 105 years (Mean = 59.2, SD = 9.4). Cognitive function declined with age net of period and cohort effects, an apparent acceleration in the rate of cognitive decline after age 65 was found adjusting for individual characteristics. Although period effects on trends in cognitive function remained stable during the study period, hierarchical APC models demonstrated significant cohort variations. Independent of age and period effects, there was a fluctuating trend across cohorts before 1960 and an overall decline across successive cohorts.ConclusionsOur study indicates that the age effect remains the most crucial factor regarding cognitive decline. Moreover, results demonstrate that cohorts living in social upheaval leading to educational deprivation and/or nutritional deficiency in early life may face a higher risk for cognitive deterioration later in life. Such findings indicate that dementia prevention from a life course perspective and cohort-specific strategies are critical to alleviating the future public-health burdens related to cognitive aging. Ongoing attention should be paid to the role of cross-cohort differences in education on cohort trends in cognition in countries like China that are aging rapidly and have a late start in educational expansion compared to other countries. Other factors, such as environmental stimulation, need to be noticed in younger cohorts.

Impact of electronic devices used at an early age on language

The acquisition of language in infants is largely the result of the process of brain maturation, as well as environmental stimulation. Currently, society is in an era of technology and use of electronic devices from an early age. The aim of this study was to demonstrate if the amount of time of use of electronic devices in children under 5 years of age affects language development. An observational, comparative, survey-type study was carried out in 269 infants of both sexes, with an age range of 6 to <60 months. The language development section of the Child Development Scale (EDI) was used. A logistic regression was performed to determine the strength of association between the factors to be studied. 269 participants were included, of which 224 (83.2%) presented their level of neurological maturation, 44 infants (16.4%) presented laged development and one (0.4%) was classified as having developmental delay. It was found that the number of daily hours that an electronic device is used behaved as a risk factor by increasing the risk of delayed language development by 1.37 times for each hour of exposure (OR: 1.37, CI95%: 1.15-1.62). It was shown that a greater number of hours of use of electronic devices is a risk factor for delayed language development in children under 5 years of age. Therefore, it is vital to limit its use in this population.

Coenzyme Q10, Vitamin E and Polyvitamin B: an exploratory double-blind randomized cross-over study in Phelan-McDermid Syndrome

Aim: Defective mitochondrial function and increased oxidative stress have been documented in Autism Spectrum Disorder (ASD) and Phelan-McDermid syndrome (PMS), one of the best-known monogenic forms of ASD. The purpose of this exploratory, double-blind, randomized cross-over trial (RCT) is to verify the efficacy and safety of a “metabolic support therapy” (MST) in PMS, while defining the experimental methodology most apt at maximizing sensitivity and reliability. Methods: A total of 31 PMS patients completed 4 months of Coenzyme Q10 (50/100 mg b.i.d.) + vitamin E (30/60 mg/d) + polyvitamin B ("active compound") vs. 4 months of only Vitamins E and B ("active comparator"). To explore their sensitivity and reliability, four primary outcome measures were used: VABS, CARS, CGI-I, and VAS. Secondary outcome measures span adaptive behaviors, social cognition, autism, problem behaviors, quality of life (QoL), communication, and comorbidities. Results: CoQ10+vit. E and B yielded significantly greater improvement in several measures of cognition and adaptive functioning, motor skills, and stereotypic behaviors compared to vit. E and B only. Maternal QoL was especially improved in the presence of CoQ10 (P &lt; 0.004). Time x Treatment interactions in CGI-I and VAS "restricted interests" scores support positive contributions also by vitamins E and B. Side effects, including hyperactivity, insomnia, and irritability, were mild, rare, and did not differ between treatment periods. Conclusion: MST may produce small-to-moderate improvement, especially in motor skills, social motivation, adaptive behaviors, responsiveness to environmental stimulation, and stereotypic behaviors in up to approximately 70% of PMS patients. A targeted confirmatory RCT contrasting Q10+vit E and B vs. inactive placebo is now warranted.

Mutant p53 leads to low-grade IFN-I-induced inflammation and impairs cGAS-STING signalling in mice.

Type I interferons (IFN-Is) are a class of proinflammatory cytokines produced in response to viruses and environmental stimulations, resulting in chronic inflammation and even carcinogenesis. However, the connection between IFN-I and p53 mutation is poorly understood. Here, we investigated IFN-I status in the context of mutant p53 (p53N236S , p53S). We observed significant cytosolic double-stranded DNA (dsDNA) derived from nuclear heterochromatin in p53S cells, along with an increased expression of IFN-stimulated genes. Further study revealed that p53S promoted cyclic GMP-AMP synthase (cGAS) and IFN-regulatory factor 9 (IRF9) expression, thus activating the IFN-I pathway. However, p53S/S mice were more susceptible to herpes simplex virus 1 infection, and the cGAS-stimulator of IFN genes (STING) pathway showed a decline trend in p53S cells in response to poly(dA:dT) accompanied with decreased IFN-β and IFN-stimulated genes, whereas the IRF9 increased in response to IFN-β stimulation. Our results illustrated the p53S mutation leads to low-grade IFN-I-induced inflammation via consistent low activation of the cGAS-STING-IFN-I axis, and STAT1-IRF9 pathway, therefore, impairs the protective cGAS-STING signalling and IFN-I response encountered with exogenous DNA attack. These results suggested the dual molecular mechanisms of p53S mutation in inflammation regulation. Our results could be helping in further understanding of mutant p53 function in chronic inflammation and provide information for developing new therapeutic strategies for chronic inflammatory diseases or cancer.

Meningkatkan Keterampilan Menggambar, Menulis, dan Membaca Anak dengan Penggunaan Sandpaper Letters [Increasing Children's Drawing, Writing, and Reading Abilities with the Usage of Sandpaper Letters

&lt;div&gt;&lt;p class="1eAbstract-text"&gt;Early drawing, writing, and reading are some good aspects that can be developed to nurture children’s language acquisition from early childhood. Environment stimulation is also one of important aspects, of which includes learning resources and teacher’s awareness of the importance of personal approach toward students. The problem that is encountered by Kindergarten 2 teachers is some students have difficulties in their early drawing, writing, and reading. This issue had brought the researcher’s attention to analyze the problem and tried to find solution, which one of them is the use of Sandpaper Letters with Montessori approach to develop early drawing, writing, and reading abilities. This research is a weak experimental research to 10 Kindergarten 2 students recommended by the homeroom teachers. The treatment used sandpaper letters with the Montessori approach for six weeks with one on one session. The result from pretest and posttest of drawing skill was N-gain 0,64 (medium), the writing skills N-gain 0,7 (high), and reading skills N-gain 0,7 (high). Based on the result, it is showed that Sandpaper letters with Montessori approach could affect the improvement of difference pace learner in early drawing, writing, and reading skills at kindergarten.&lt;/p&gt;&lt;/div&gt;