Screening Results Research Articles

Abstract B042: Feasibility of an electronic medical records based ovarian cancer symptom screening patient questionnaire

Abstract B042: Feasibility of an electronic medical records based ovarian cancer symptom screening patient questionnaire

Prenatal mental health and emotional experiences during the pandemic: associations with infant neurodevelopment screening results.

This study determined whether parental mental health and emotional experiences during the prenatal period were linked to infant developmental outcomes through the Ages and Stages Questionnaire (ASQ-3) at 8-10 months. Participants included 133 individuals who were living in the US and were pregnant or had given birth within 6 months prior to enrollment. Respondents were majority White with high education and income levels. Online surveys were administered from May 2020 to September 2021; follow-up surveys were administered from November 2020 to August 2022. Parent generalized anxiety symptoms were positively associated with infant communication (β = 0.34, 95% CI [0.15, 1.76], p < 0.05), while parent-fetal bonding was positively associated with infant communication (β = 0.20, 95% CI [0.05, 0.76], p < 0.05) and personal-social performance (β = 0.20, 95% CI [0.04, 0.74], p < 0.05). COVID-19-related worry was negatively associated with infant communication (β = -0.30, 95% CI [-0.75, -0.12], p < 0.05) and fine motor performance (β = -0.25, 95% CI [-0.66, -0.03], p < 0.05). Parent mental health and emotional experiences may contribute to infant developmental outcomes in high risk conditions such as a pandemic. Maternal SARS-CoV-2 infection has been evaluated in relation to child outcomes, however, parent psychosocial experiences should not be overlooked when considering pandemic risks to child development. Specific prenatal mental health and pandemic-related emotional experiences are associated with infant developmental performance, as assessed by the Ages and Stages. Questionnaire (ASQ-3) at 8 to 10 months old. Findings indicate that parental prenatal anxiety and emotional experiences from the pandemic should be assessed when evaluating child developmental delays.

Using timeliness metrics for household contact tracing and TB preventive therapy in the private sector, India.

<sec id="st1"><title>BACKGROUND</title>Although screening of household contacts (HHCs) of TB patients and provision of TB preventive therapy (TPT) is a key intervention to end the TB epidemic, their implementation globally is dismal. We assessed whether introducing a '7-1-7' timeliness metric was workable for implementing HHC screening among index patients with pulmonary TB diagnosed by private providers in Chennai, India, between November 2022 and March 2023.</sec><sec id="st2"><title>METHODS</title>This was an explanatory mixed-methods study (quantitative-cohort and qualitative-descriptive).</sec><sec id="st3"><title>RESULTS</title>There were 263 index patients with 556 HHCs. In 90% of index patients, HHCs were line-listed within 7 days of anti-TB treatment initiation. Screening outcomes were ascertained in 48% of HHCs within 1 day of line-listing. Start of anti-TB treatment, TPT or a decision to receive neither was achieved in 57% of HHC within 7 days of screening. Overall, 24% of screened HHCs in the '7-1-7' period started TPT compared with 16% in a historical control (P < 0.01). Barriers to achieving '7-1-7' included HHC reluctance for evaluation or TPT, refusal of private providers to prescribe TPT and reliance on facility-based screening of HHCs instead of home visits by health workers for screening.</sec><sec id="st4"><title>CONCLUSIONS</title>Introduction of a timeliness metric is a workable intervention that adds structure to HHC screening and timely management.</sec>.

Оценка влияния ретроцеребеллярных кист головного мозга на ликворную систему как критерий годности к летной работе

Retrocerebellar cysts of the brain represent the aspect that is important for determination of fitness for flight. The study was aimed to assess their impact on the pilot performance by conducting comparative analysis of MRI data of the first-year cadets and experienced pilots. We assessed the prevalence of retrocerebellar cysts among cadets and pilots, conducted non-contrast brain MRI, and compared the major academic and physical performance indicators, along with the results of professional psychological screen. The prevalence of retrocerebellar cysts among first-year cadets was 8.2%. High prevalence of asymptomatic retrocerebellar cysts among experienced pilots was revealed (two cases out of five). The intergroup comparison of indicators makes it possible to draw a conclusion about probable minor impact of such changes on fitness for flight. Further research is required to clarify the mechanisms underlying the impact of retrocerebellar cysts on the pilot performance and develop appropriate guidelines for medical boards.

Screening and Recognition of Cognitive Impairment in Older People Visiting Hearing Aid Dispensers in the Netherlands

ObjectivesThis study aims to determine how prevalent suspected cognitive impairment is in older people visiting hearing aid dispensers, and to assess whether hearing aid dispensers’ judgment on cognition was in accordance with the outcome of a cognitive screening. DesignThis observational study was conducted between April and May 2022. Setting and ParticipantsFour private hearing aid retail stores in the Netherlands, where cognitive impairment was screened in people aged ≥60 years. MethodsThe Mini-Cog was used for cognitive screening. In addition, hearing aid dispensers were asked to provide their professional judgment if they suspected cognitive impairment. ResultsOf the total 239 older individuals screened, 133 were men [56%, mean age: 79 years (SD 8.6)], and 51 (21.3%) had abnormal outcomes on the Mini-Cog test. The recognition of possible cognitive impairment by the hearing aid dispensers compared to the outcome of the Mini-Cog resulted in correct predictions for 183 of the 239 individuals. Conclusion and ImplicationsCognitive screening in hearing-impaired older adults who visit a hearing aid dispenser suggests that cognitive impairment might be present in approximately 1 in 5 individuals. Hearing aid dispensers' response to the presence of a cognitive impairment was in 2 of 3 in accordance with an abnormal outcome on cognitive screening. To improve hearing care for people with cognitive impairment, it might be important to enhance hearing care professionals’ recognition of cognitive impairment in older individuals.

Making it "EASI" for pediatricians to determine when toddler tantrums are "more than the terrible twos": Proof-of-concept for primary care screening with the Multidimensional Assessment Profiles-Early Assessment Screener for Irritability (MAPS-EASI).

Up to 20% of youth have impairing mental health problems as early as age 3. Early identification and intervention of mental health risks in pediatric primary care could mitigate this crisis via prevention prior to disease onset. The purpose of this study was to establish the feasibility and acceptability of implementing a brief transdiagnostic screening instrument in pediatric primary care for irritability and corollary impairment. Five pediatric clinicians in a Midwest clinic implemented the Multidimensional Assessment Profiles-Early Assessment Screener of Irritability (MAPS-EASI) for toddlers (24-30 months) and their families. MAPS-EASI (psychometrically derived from the well-validated MAPS-Scales) includes six items (scored 0-5) about symptoms (e.g., tantrums, grumpy mood), context, and frequency and two items (scored 0-3) assessed impairment. Positive screens (MAPS-EASI ≥ 5 plus impairment ≥ 2) were referred to an evidence-based parenting intervention. We assessed reach and outcomes of MAPS-EASI screening. Follow-up interviews with clinicians assessed perspectives on irritability screening and MAPS-EASI implementation. Of 201 eligible families, 100 (49.8%) completed the screener for a 24- or 30-month well-child visit. Mean MAPS-EASI scores were 5.8 (SD = 3.2), mean impairment scores were 0.9 (SD = 0.9), and 24 (24.0%) screened positive. Clinicians indicated that irritability screening for toddlers was aligned with their prevention-oriented, developmentally based practice. MAPS-EASI had face validity and increased clinician decision-making confidence. Finally, clinicians identified barriers and facilitators to large-scale implementation. MAPS-EASI proved to be feasible and acceptable in pediatric primary care. Further tailoring will be needed as the MAPS-EASI processes are scaled out to new contexts and populations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Guidelines toward more socially just mental health screening in schools.

Mental health screening is a pivotal practice for promoting the social-emotional-behavioral (SEB) health and well-being of youth in schools. However, some aspects of traditional mental health screening practices may inadvertently perpetuate structural racism and unintentionally facilitate oppression and SEB disparities. We address this issue constructively by presenting an intentional approach to guide school psychologists and related professionals in implementing more socially just mental health screening in schools. Our guidelines are grounded within the four phases of the Participatory Culture-Specific Intervention Modeling (PCSIM) framework: system entry, culture-specific model development, culture-specific program development, and program continuation or extension. We propose that conceptualizing mental health screening within PCSIM methodology promotes more socially just practices by (a) displacing the implicit power of professionals, (b) giving transparent representation to local communities, and (c) employing methods that are recursive, culturally relevant, and intended to build capacity for sustained transformative change. Within each PCSIM phase, we recommend culturally responsive practices for professionals that foster equity in screening and SEB outcomes and discuss ways to resist practices that perpetuate oppression and disparities. We aim to convey a method for mental health screening that is not done to students and schools but rather done in partnership with and for the benefit of students and schools. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Utilizing Artificial Intelligence in the Development of Medicinal Drugs: Practical Applications

The COVID-19 pandemic has underscored the critical need for innovative drug discovery methods. The journey from conceptualizing a drug to its clinical application is fraught with potential pitfalls, including extensive complexity, significant expenses, and a high risk of failure. Recent years have witnessed remarkable advancements in technologies such as cloud computing, GPUs, and TPUs. These developments, coupled with the surge in medical data availability and the emergence of deep learning, present an unprecedented opportunity to enhance drug discovery processes. By leveraging artificial intelligence (AI) to analyze vast amounts of data-from extensive molecular screening outcomes to individual health records and public health data-the efficiency of the drug discovery pipeline could be significantly improved, minimizing the likelihood of failure. This paper explores the application of AI in various phases of drug development, including the use of computational strategies for de novo drug design and the prediction of drug properties. We address challenges associated with molecular representation, data acquisition, complexity, and the inconsistencies in labeling across open-source databases and AI-powered tools that support drug discovery efforts. Furthermore, we examine the role of advanced AI techniques, such as graph neural networks, reinforcement learning, generative models, and structure-based methods like molecular docking and dynamics simulations, in enhancing drug discovery and evaluating drug efficacy.

Discrete element simulation of vibration compaction of slag subgrade

In this study, to improve the compaction quality and parameters of slag, discrete element models of irregular rock particles (10–60 mm) and circular soil particles (5 mm) were established based on on-site slag screening results. The motion of the vibratory roller was captured by coupling the roadbed model with the roller model in a simulation in which the roller vibrated and compacted the slag subgrade. The results indicated that (1) the best compaction was achieved when the small particle content was 40%, the medium particle content was 20%, and the large particle content was 40%. (2) When the slag was dominated by small rock particles, the optimum compaction frequency was 28 Hz, and when large rock particles dominated, the optimum compaction frequency was 33 Hz. (3) Rock particles were the primary particles that experienced stress in the vibration compaction, and the compressive force and displacement depended on the particle size. (4) The longitudinal and vertical displacements and rotation angles of the soil and rock particles were examined. The results of this study are conducive for advancing the understanding of slag compaction and improving the working efficiency and compaction quality of rollers.

Comprehensive evaluation and screening identification indexes of heat‐resistance indices in cotton (Gossypium hirsutum L.)

AbstractCotton (Gossypium hirsutum L.) cultivars exhibit varying responses to heat stress. To investigate the heat resistance of various cotton and establish an index system for evaluating their heat resistance, 21 cotton cultivars were selected and subjected to two temperature regimes (CK, average temperature 28°C, 32/24°C; HT, average temperature 38°C, 42/34°C). The results showed that under high temperatures, different changes occurred in individual indexes of cotton, reflecting the differences in heat resistance in cotton cultivars. A total of 21 cotton cultivars could be classified into four types: heat‐tolerant, moderate heat‐tolerant, moderate heat‐sensitive and heat‐sensitive cultivars by multivariate statistical analysis. Moreover, the indexes of net photosynthetic rate (Pn), leaf superoxide dismutase activity (LSOD), the maximum photochemical quantum yield (Fv/Fm), the actual photochemical quantum yield (ΦPSII), leaf malondialdehyde content (LMDA), leaf catalase activity (LCAT), dry matter weight of shoot (SDW) and root malondialdehyde content (RMDA) were determined to be useful for evaluating the cotton heat tolerance by stepwise regression analysis. The pot experiment showed that the reduction of boll number, boll weight and seed cotton yield was more remarkable under HT in the heat‐sensitive cultivar CCRI‐92 than in the heat‐resistant cultivar CCRI‐69, which further verified the screening results. In conclusion, the heat‐sensitive cultivars CCRI‐92 and heat‐resistant cultivar CCRI‐69 which are identified by seedling experiment could serve as ideal experimental materials for studying heat resistance in cotton. The physiological indices such as Pn, LSOD, Fv/Fm, ΦPSII, LMDA, LCAT, SDW and RMDA be employed for assessing the heat tolerance in cotton.

The feasibility of population screening for paroxysmal atrial fibrillation using hand-held electrocardiogram devices.

There are few data on the feasibility of population screening for paroxysmal atrial fibrillation (AF) using hand-held electrocardiogram (ECG) devices outside a specialist setting or in people over the age of 75. We investigated the feasibility of screening when conducted without face-to-face contact ('remote') or via in-person appointments in primary care and explored impact of age on screening outcomes. People aged ≥65 years from 13 general practices in England participated in screening during 2019-20. This involved attending a practice nurse appointment (10 practices) or receiving an ECG device by post (three practices). Participants were asked to use a hand-held ECG for 1-4 weeks. Screening outcomes included uptake, quality of ECGs, AF detection rates, and uptake of anticoagulation if AF was detected. Screening was carried out by 2141 (87.5%) of people invited to practice nurse-led screening and by 288 (90.0%) invited to remote screening. At least 56 interpretable ECGs were provided by 98.0% of participants who participated for 3 weeks, with no significant differences by setting or age, except people aged 85 or over (91.1%). Overall, 2.6% (64/2429) screened participants had AF, with detection rising with age (9.2% in people aged 85 or over). A total of 53/64 (82.8%) people with AF commenced anticoagulation. Uptake of anticoagulation did not vary by age. Population screening for paroxysmal AF is feasible in general practice and without face-to-face contact for all ages over 64 years, including people aged 85 and over.

Experiences of women participating in a human papillomavirus-based screen-triage-and treat strategy for cervical cancer prevention in Malawi.

To explore the experiences of Malawian women who underwent a human papillomavirus (HPV)-based screen-triage-treat algorithm for cervical cancer (CxCa) prevention. This algorithm included GeneXpert® HPV testing of self-collected vaginal samples, visual inspection with acetic acid (VIA) and colposcopy for HPV-positive women, and thermal ablation of ablation-eligible women. In-depth interviews were conducted with participants of a trial that evaluated the feasibility of a HPV-based screen-triage-treat algorithm among women living with HIV and HIV negative women in Lilongwe, Malawi. Participants were recruited from 3 groups: 1) HPV-negative; 2) HPV-positive/VIA-negative; 3) HPV-positive/VIA-positive and received thermal ablation. Interviews explored baseline knowledge of CxCa and screening, attitudes towards self-collection, and understanding of test results. Content analysis was conducted using NVIVO v12. Thematic saturation was reached at 25 interviews. Advantages of HPV self-collection to participants were convenience of sampling, same-day HPV results and availability of same-day treatment. There was confusion surrounding HPV-positive/VIA-negative results, as some participants still felt treatment was needed. Counseling, and in particular anticipatory guidance, was key in helping participants understand complex screening procedures and results. Overall, participants expressed confidence in the HPV screen-triage-treat strategy. HPV testing through self-collected samples is a promising tool to increase CxCa screening coverage. A multi-step screening algorithm utilizing HPV self-testing, VIA triage and thermal ablation treatment requires proper counseling and anticipatory guidance to improve patient understanding. Incorporating thorough counseling in CxCa screening programs can change women's perspectives about screening, build trust in healthcare systems, and influence healthcare seeking behavior towards routine screening and prevention.

Fish predation risk alters the microbiota of Daphnia in the process of inducing its life‐history defence traits

Abstract Host‐associated microbiota is an essential mediator of host adaptation to changeable environmental conditions. However, whether fish predation risk alters the gut microbiota composition of Daphnia while also of inducing Daphnia's life‐history defence traits remains unclear. Examination of the effect of predation risk on prey‐associated microbiota may help in improving our understanding of induced anti‐predation defence from a microbial perspective. In this study, Daphnia magna was used as the model organism to investigate the changes in the microbiota in the gut of Daphnia as well as in the whole Daphnia and the culture medium during D. magna life‐history anti‐predation defence. The relationship of these changes with the development stage was also assessed. The results showed that predation risk can simultaneously induce anti‐predation defences and reshape the associated microbiota composition of Daphnia. The gut microbiota of D. magna responded to both developmental stages and predation risk. The Shannon diversity of gut microbiota under predation risk decreased significantly with developmental stage. The abundance of dominant bacteria such as Burkholderiaceae and Flavobacteriaceae decreased under predation risk and was further reduced with developmental stage. Functional prediction results showed that the presence of predation risk mainly weakened overall microbial function, especially metabolic function, in the gut of D. magna. The weakening of microbial function was most obvious during sexual maturity. In addition, the number of unique operational taxonomic units in the whole Daphnia and dissected guts under predation risk was significantly higher than those in control. Based on the screening results, the Pantoea genus (Erwiniaceae family) can clearly distinguish dissected gut samples with or without predation risk. The present study provided more insights into the structural features and functional roles of the Daphnia microbiota and improved our understanding of induced anti‐predation defence from a microbial perspective. Furthermore, this study highlights the possible complex correlations that exist between induced defensive traits and altered microbiota, which warrants further investigation.

Meconium Peritonitis in the Newborn with Cystic Fibrosis and Negative Neonatal Screening for Immunoreactive Trypsinogen: Clinical Case

Background. Meconium ileus is one of the manifestations of cystic fibrosis. It is characterized by intestinal obstruction with viscous meconium leading to perforation and peritonitis. The issues of early diagnosis of cystic fibrosis, management of newborns with meconium ileus and negative neonatal screening for immunoreactive trypsinogen (IRT), as well as IRT decrease causes and mechanisms in patients with meconium ileus require further study. Clinical case description. Routine ultrasound examination at the 33rd week of gestation has shown signs of colon obstruction and meconium peritonitis in the intrauterine child. Surgical treatment of peritonitis was performed urgently on the 1st day after birth. The child was on mechanical ventilation from the 1st day of life. The child has shown signs of intrahepatic cholestasis with direct hyperbilirubinemia (up to 100 μmol/L) and signs of hemorrhagic syndrome (bleeding from injection sites) on the 8th day of life. Negative IRT blood test was received (21.6 ng/mL, normal value &lt; 70 ng/mL) on the 10th day. The fecal elastase concentration was 45 μg/g (normal value &gt; 200 μg/g) (on the same day). Sweat tests were performed on the 21st and 23rd days of life. They have shown high levels of sweat chlorides (112 mmol/L in both samples, normal value — 30–59 mmol/L). The diagnosis of «cystic fibrosis» was established, thus, dornase alfa (dosage — 2.5 mg/day) was added to the therapy. Conclusion. Meconium ileus is one of the specific intestinal manifestations of cystic fibrosis and it commonly can be complicated with intestinal perforation in the intrauterine child with further peritonitis. Children with meconium ileus require sweat tests regardless the neonatal screening results.

Critical congenital heart disease: contemporary prenatal screening performance and outcomes in a multi-centre perinatology service

BackgroundPrenatal detection of critical congenital heart disease (CCHD) optimises perinatal decision-making and neonatal outcomes. The objective of this study was to determine the prenatal screening performance, care pathways and perinatal outcomes for prenatally and postnatally diagnosed cases of CCHD over a four-year period.Study designThis retrospective cohort study in a tertiary centre and its two affiliated secondary sites examined all cases of CCHD, including cases of pregnancy termination and in-utero fetal death, neonatal death and liveborn babies that underwent cardiac catheterization or surgery in the first six weeks of life. Prenatal and postnatal data were ascertained from the first trimester assessment for all patients diagnosed prenatally. Cases requiring intervention that were first identified in the postnatal period were included to determine prenatal detection rates. Follow-up for all cases of CCHD continued to one year of age.ResultsIn a consecutive cohort of 49,950 pregnancies in a 4-year period 01/2019 to 12/2022, a prenatal diagnosis of CCHD was made in 96 cases, yielding a prevalence of 1.9 per 1000 births. The prenatal detection for right duct-dependant heart pathology and congenital heart block was 100%, 85% for left duct-dependant pathology and 93% for transposition of the great arteries (TGA). In the prenatally diagnosed group, 37% of cases were complicated by extracardiac structural abnormalities, a genetic diagnosis or both. All cases of prenatal detection were identified in the context of routine anatomy screening rather than specialist Fetal Cardiac screening services. Almost half of all pregnancies complicated by CCHD did not undergo neonatal cardiac intervention, by virtue of parental choice determined either prenatally or after birth. An additional eight babies were diagnosed with CCHD in the neonatal period, such that the prenatal detection rate for CCHD was 92% (96/104, 95% CI = 84%-96%). Survival at 1-year for infants deemed suitable for CCHD surgery was 85%.ConclusionIn a large unselected population, optimal rates of prenatal detection of critical congenital heart disease can be achieved by a protocolised approach to mid-trimester fetal anatomy ultrasound, underpinned by a programme of sonographer education and training. The cardiac abnormalities most likely to evade prenatal detection are left-sided obstructive lesions.

Phenotypic and Genotypic Criteria for the Screening of Highly Active S-Type Pyocins Pseudomonas aeruginosa Producers

Bacteriocins of Pseudomonas aeruginosa, especially S-type pyocins, show high efficiency as analogs of antimicrobial drugs. Various screening methods can be used to identify producers of highly active pyocins, but there are no clear criteria for selecting perspective strains. The aim of this work was to determine criteria that can be used during phenotypic and genotypic screening for the selection of perspective highly active S-type pyocin P. aeruginosa producers. Methods. The objects of investigation were 40 P. aeruginosa strains. Pyocins were obtained from each culture, relative coefficients of activity spectrum and sensitivity were determined for all the strains used. The obtained results of the phenotypic screening were compared with the data of the genotypic screening. Results. The use of the proposed method of activity assessment according to the lysis intensity made it possible to phenotypically assess the expression of pyocin genes. It was established that according to the new criteria, only one strain — P. aeruginosa UCM B-333 — can be included in the group of the most active pyocin producers that inhibit the growth of more than 75% of indicator cultures. The majority of representatives of maximally and highly active producers were characterized by high resistance to the action of other pyocins, which can be considered as an additional criterion for the selection of perspective strains. During genotypic screening, it was established that the quantity of pyocin genes in the genome cannot be interpreted as a clear criterion of the producer’s perspective. However, 50% of representatives of maximally and highly active pyocin producers were characterized by the presence of two pyocin genes, while in 47.7% of moderately active and 54.5% of low active producers, one pyocin gene was detected more often. It was established that with widening the bacteriocin activity spectrum, the detection frequency of pyocin S1 and S5 genes increases, and for pyocin S2 and S3 genes — decreases. Thus, among the producers of maximally and highly active bacteriocins, pyocin S1 and S5 genes were identified with the highest frequency — 42.8% and 78.6%, and pyocin S2 and S3 genes — with the lowest one — 28.6% and 7.1%, respectively. Gene of pyocin S4 with tRNase activity were detected with equally high frequency in all groups of producers. Conclusions. The method of activity assessment by the lysis intensity allows not only to determine the presence of pyocins, but also to phenotypically evaluate the level of their expression, which is an important criterion for the selection of perspective producers. Bacteriocins with a wider activity spectrum are synthesized by P. aeruginosa strains with higher resistance to the action of pyocins from other cultures. The most optimal genotypic criterion for the selection of a highly perspective pyocin producer, detection of genes combination of bacteriocins with different mechanisms of action — with DNase activity (pyocin S1) and the ability to pore formation (pyocin S5) — can be considered.

Shifting the pH profiles of Staphylococcus epidermidis lipase (SEL) and Staphylococcus hyicus lipase (SHL) through generating chimeric lipases by DNA shuffling strategy.

Enzymes are often required to function in a particular reaction condition by the industrial procedure. In order to identify critical residues affecting the optimum pH of Staphylococcal lipases, chimeric lipases from homologous lipases were generated via a DNA shuffling strategy. Chimeric 1 included mutations of G166S, K212E, T243A, H271Y. Chimeric 2 consisted of substitutions of K212E, T243A, H271Y. Chimeric 3 contained substitutions of K212E, R359L. From the screening results, the pH profiles for chimeric 1 and 2 lipases were shifted from pH 7 to 6. While the pH of chimeric 3 was shifted to 8. It seems the mutation of K212E in chimeric 1 and 2 decreased the pH to 6 by changing the electrostatic potential surface. Furthermore, chimeric 3 showed 10 ˚C improvement in the optimum temperature due to the rigidification of the catalytic loop through the hydrophobic interaction network. Moreover, the substrate specificity of chimeric 1 and 2 was increased towards the longer carbon length chains due to the mutation of T243A adjacent to the lid region through increasing the flexibility of the lid. Current study illustrated that directed evolution successfully modified lipase properties including optimum pH, temperature and substrate specificity through mutations, especially near catalytic and lid regions.

Genetic Information to Share with Parents when Newborn Screening Reveals the Presence of Sickle Cell Trait.

The primary purpose of newborn screening for sickle cell disease is to diagnose the disease before the appearance of symptoms and to initiate early treatment. To answer the question "What genetic information needs to be communicated to parents when newborn screening reveals the presence of a sickle cell trait," we conducted a survey using a self-administered online questionnaire. We received responses from 122 healthcare workers and members of sickle cell disease associations, in France and French overseas departments. Our results showed similar positions on this issue. The information conveyed is not consistent and is the result of grassroots initiatives. The negative consequences generated by this information could be reduced when this information is delivered by a multidisciplinary team, within the framework of a dedicated consultation. This information on sickle cell trait status should be given in at least three key periods: the neonatal period, early adolescence, and later adolescence, when reproductive implications become important. Neonatal screening programs should develop systems that allow referring physicians to easily access the results of neonatal screening electronically. Harmonization of practices should allow a better analysis of the consequences of this counselling on family projects.

New 2-oxoindole derivatives as multiple PDGFRα/ß and VEGFR-2 tyrosine kinase inhibitors

Two new series of N-aryl acetamides 6a-o and benzyloxy benzylidenes 9a-p based 2-oxoindole derivatives were designed as potent antiproliferative multiple kinase inhibitors. The results of one-dose NCI antiproliferative screening for compounds 6a-o and 9a-p elucidated that the most promising antiproliferative scaffolds were 6f and 9f, which underwent five-dose testing. Notably, the amido congener 6f was the most potent derivative towards pancreatic ductal adenocarcinoma MDA-PATC53 and PL45 cell lines (IC50 = 1.73 µM and 2.40 µM, respectively), and the benzyloxy derivative 9f was the next potent one with IC50 values of 2.85 µM and 2.96 µM, respectively. Both compounds 6f and 9f demonstrated a favorable safety profile when tested against normal prostate epithelial cells (RWPE-1). Additionally, compound 6f displayed exceptional selectivity as a multiple kinase inhibitor, particularly targeting PDGFRα, PDGFRβ, and VEGFR-2 kinases, with IC50 values of 7.41 nM, 6.18 nM, and 7.49 nM, respectively. In contrast, the reference compound Sunitinib exhibited IC50 values of 43.88 nM, 2.13 nM, and 78.46 nM against the same kinases. The derivative 9f followed closely, with IC50 values of 9.9 nM, 6.62 nM, and 22.21 nM for the respective kinases. Both 6f and 9f disrupt the G2/M cell cycle transition by upregulating p21 and reducing CDK1 and cyclin B1 mRNA levels. The interplay between targeted kinases and these cell cycle regulators underpins the G2/M cell cycle arrest induced by our compounds. Also, compounds 6f and 9f fundamentally resulted in entering MDA-PATC53 cells into the early stage of apoptosis with good percentages compared to the positive control Sunitinib. The in silico molecular-docking outcomes of scaffolds 6a-o and 9a-p in VEGFR-2, PDGFRα, and PDGFRβ active sites depicted their ability to adopt essential binding interactions like the reference Sunitinib. Our designed analogs, specifically 6f and 9f, possess promising antiproliferative and kinase inhibitory properties, making them potential candidates for further therapeutic development.

Correlation Between Life Satisfaction and Symptoms of ADHD in Dental Students: The Mediation of Resilience.

This study explores the correlation between life satisfaction and ADHD symptoms. It also discusses whether resilience mediates the correlation between ADHD symptoms and life satisfaction. We surveyed 297 dental students. A total of 291 completed a self-report scale consisting of the Adult ADHD Self-Report Scale, Wender Utah Rating Scale, Life Satisfaction Scale, and Conner-Davidson Resilience Scale. The study used hierarchical linear regression analysis, resampling, and asymptotic strategies for data processing. The ADHD screening results of the self-report scale were positive for 6.87% of the students. This positive rate differed among participants of diverse ages and varying paternal education levels. ADHD symptoms were negatively correlated with life satisfaction and resilience. Life satisfaction was observably positively associated with resilience. Resilience serves as a mediating role between life satisfaction and the two symptoms of ADHD. Resilience intervention programs can enhance the life satisfaction of dental students, especially those with positive ADHD symptoms screening.